- SpongeBob SquarePants
- Off-Model SpongeBob (debut)
- Squidward Tentacles (cameo)
- Gnarly Squid (debut)
- Eugene H. Krabs
- Sheldon J. Plankton
- Ideal Plankton (debut)
- Karen Plankton
- Virus (debut)
- Female hick (debut)
- Hanna (debut)
- Robot SpongeBob (cameo)
- Plankton's cousins (cameo)
- Old Man Jenkins (cameo)
- Lily Plankton (cameo)
- King Neptune (mentioned)
- Incidental 69
- Incidental 68
- Nat Peterson
- Incidental 67
The episode starts with Karen obtaining a virus due to hanging out with a sick computer. Plankton sees this and needs someone stupid enough to want to fix her, and just at the right time, SpongeBob is next to the Chum Bucket. After deciding that the mission will be called Operation: Save Karen, Plankton transports SpongeBob into Karen to defeat the virus.
Plankton gives SpongeBob directions on how to find the virus and soon after he starts looking for it, he falls down into a hole the virus made and sees it eat through Karen. Meanwhile, Karen becomes completely delusional and escapes the Chum Bucket into the Krusty Krab, where she causes chaos. SpongeBob flings back up onto the surface of the inside of Karen and continues searching for destruction caused by the virus, but accidentally activates the security button. Thankfully, before he gets shot by a laser, he is saved by Ideal Plankton, who is what Karen pictures Plankton as.
As the virus continues destroying parts of Karen, Ideal Plankton and SpongeBob confront different characters how Karen sees them, and gets into a battle with them. After they defeat them, the two see the virus on the other side of a trench. SpongeBob uses a rope to cross the trench, but when Ideal Plankton tries to cross, part of the ground breaks and he falls into the trench, forcing SpongeBob to have to save Karen by himself.
Karen is shown driving a car to a party at Wagon Wheel due to how delusional she is. Inside Karen, the virus is shown to be eating Karen's memories, prompting SpongeBob to try and defeat it. After his attempts fail, he gets so scared he breaks into pieces. When he goes back into normal form, he winds up with one extra piece and throws it onto the ground. The virus eats this, telling SpongeBob that the virus is simply hungry. The episode ends with SpongeBob taking out the virus from Karen and letting him eat a Krabby Patty to satisfy how hungry it is.
|( ‣ ) Associated production music|
|( • ) Original music|
|( ◦ ) SpongeBob music|
‣ One Zero Zero - Harry Breuer, Jean-Jacques Perrey [Title card]
‣ Happy Links 6-9 - Paul Fenoulhet [Karen and Hanna at the Chum Bucket]
‣ Happy Links 1-5 - Paul Fenoulhet [Karen sneezes at Plankton]
‣ Oh My Trill! - [ProjectSAM Symphobia Colours: Animator] [Karen starts malfunctioning]
‣ Uh Oh Flutter-Eyed - [ProjectSAM Symphobia Colours: Animator] [Karen crashes into a wall]
• Hot Steel and Slide Licks (i) - Jeremy Wakefield ["Uh-oh. My ones and zeroes look like 10, 10, 10, 10."]
‣ Mission Improbable - Nicolas Carr, Barry Anthony ["Someone's gonna have to get inside you and kill that virus."]
‣ Seaweed - Steve Belfer [SpongeBob knocking Chum Bucket door with a hammer]
‣ In Disguise Ensemble - [ProjectSAM Symphobia Colours: Animator] [Plankton tells SpongeBob that Karen needs his help]
‣ Phrases - Is It Jazz - [ProjectSAM Symphobia Colours: Animator] ["♪Who lives in a crabapple under a pea♪"]
‣ Lap Steel - Nicolas Carr [Transition to next scene]
‣ Phrases - Is It Jazz - [ProjectSAM Symphobia Colours: Animator] ["♪Observant and yellow fellow is he♪"]
‣ ? ["Journey to the Center of Karen."]
‣ Arnold is Back 2 - Gregor Narholz ["The Mainframe Mission."]
‣ Harp Ding - Nicolas Carr ["Ooh, I know!"]
‣ Glory Road - Sam Fonteyn ["Operation: Save Karen!"]
‣ Toy Piano - Nicolas Carr, Barry Anthony [SpongeBob holds up a drawing]
‣ Hot Steel and Slide Licks - Jeremy Wakefield [Chum Bucket exploded]
‣ Laughter Muted Trumpet - [ProjectSAM Symphobia Colours: Animator] [Plankton blows the fire out on his antennas]
‣ Neutral Mood - Simon May [SpongeBob zapped and injected into Karen]
‣ In Disguise Ensemble - [ProjectSAM Symphobia Colours: Animator] ["Get away."]
‣ Uh Oh Flutter-Eyed - [ProjectSAM Symphobia Colours: Animator] [Plankton gets electrocuted]
‣ Space Trek - Philip Johnston, Norman Whittle [SpongeBob arrives at Karen's hard drive]
‣ Destination Unknown - Gregor Narholz [Plankton starts talking to SpongeBob via megaphone]
‣ Tiptoe Quick Peek - [ProjectSAM Symphobia Colours: Animator] ["Talk to me, you digitized doofus!"]
‣ Tiptoe Footsteps - [ProjectSAM Symphobia Colours: Animator] ["Plankton, I do not respond to insults."]
‣ Destination Unknown - Gregor Narholz [Plankton tells SpongeBob to look for destruction]
‣ Monster Movie Orchestra - Steve Sechi, Kostas Varotsis [SpongeBob falls through a hole made by the virus]
‣ Monster Bug A - Gregor Narholz [Karen gets off the table and starts destroying the Krusty Krab]
‣ Melodramatic Moments - Michael Bolger, Nicolas Carr ["I need you to control your wife. Er, computer, or whatever."]
• Hot Steel and Slide Licks (j) - Jeremy Wakefield [Karen throws Squidward away and climbs into the register boat]
‣ Melodramatic Moments - Michael Bolger, Nicolas Carr [Krabs grabs the cash register out of Karen]
• Hot Steel and Slide Licks (o) - Jeremy Wakefield ["Wow, I can never un-see that."]
‣ Code "Dead End" - Gregor Narholz [SpongeBob wandering through the hard drive]
‣ Odyssey - Sam Spence [Ideal Plankton appears and blasts the lasers with a laser gun]
‣ Comedy Punctuations and Bridges 3 - Fredric Bayco [SpongeBob sighs and skips]
‣ Fun of the Fair - David Farnon [Amusement park in Karen's hard drive]
‣ Musique De L'Infini - Jean-Jacques Perrey [Virus destroys Karen's anger control center and love center]
‣ Odyssey - Sam Spence [Ideal Plankton climbs up a wall with SpongeBob]
‣ Unknown Track 72 - Money Krabs appears
‣ ? [Gnarly Squid appears]
• Hot Steel and Slide Licks (f) - Jeremy Wakefield ["Hmm? Uh, nothing like a little make-up couldn't fix."]
‣ ? [Off Model SpongeBob appears]
‣ Armed Attack - Jean Clero [Ideal Plankton fights Money Krabs and Gnarly Squid]
‣ ? [Both SpongeBobs babbling]
‣ Code "Dead End" - Gregor Narholz ["Neptune's network! Which one of you is the real SpongeBob?"]
‣ Unknown Track 72 - SpongeBob claps
‣ Musique De L'Infini - Jean-Jacques Perrey [Virus roars to SpongeBob and Ideal Plankton]
‣ Thrill Ride - Gregor Narholz [SpongeBob swings across a ravine]
‣ Tower of Evil - Magnum Opus [Ideal Plankton falls into the ravine]
‣ Odyssey - Sam Spence ["I mean, yes!"]
• SpongeBob Theme II - Nicolas Carr, Sage Guyton, Jeremy Wakefield [Karen driving crazily a boat with Plankton]
‣ Hillbilly Party - Nicolas Carr, Sage Guyton, Jeremy Wakefield [Karen crashes the boat into Wagon Wheel]
‣ On Fire - Gregor Narholz [Virus at Karen's memory bank/SpongeBob escapes from virus until he bumps into a brick wall]
‣ Vibe Sting - Nicolas Carr ["I always wind up with one extra piece."]
‣ One Zero Zero - Harry Breuer, Jean-Jacques Perrey [Virus eats SpongeBob's extra piece]
• Hot Steel and Slide Licks (p) - Jeremy Wakefield [Karen is tired and shuts off]
• Earl's Revenge - Sage Guyton, Jeremy Wakefield [Ending]
- This episode is available on the SpongeBob SquarePants Vol. 19 and The Complete Eleventh Season DVDs.
- This and "Girls' Night Out" are the first episodes to premiere on a day that daylight saving time ends in the United States.
- This episode was paired up with "Girls' Night Out" during the original American airing, but has since been re-airing with "Appointment TV."
- In the UK, Plankton's line, "It's probably a suicide mission" was removed due to "suicide" being an inappropriate word.
- Karen sings a warped version of the SpongeBob SquarePants theme song in her delusional state.
- This episode was originally going to premiere on October 24, 2018, before the new president of Nickelodeon signed on, at which it was moved to November 4, 2018.
- When SpongeBob gets mixed up after he is charred by the virus, he resembles how he does at one point in the theme song sequence.
- The flashbacks in Karen's memory includes footage from "Plankton!," "Welcome to the Chum Bucket," "The Algae's Always Greener," "Plankton's Army," "Enemy In-Law," "Komputer Overload," "Salsa Imbecilicus," "Plankton Gets the Boot," and "F.U.N."
- The fourth wall is broken twice in this episode:
- Karen throws a boat in the sky, hitting and knocking down one of the flower clouds.
- Karen sings a warped version of the theme song in her delusional state.
- This marks the first usage of the APM track "On Fire" since "Banned in Bikini Bottom" and "Arnold is Back 2" since "Patty Hype."
- This is the second SpongeBob SquarePants production that involves CGI, in this episode, it's inside Karen. The first production is The SpongeBob Movie: Sponge Out of Water.
- SpongeBob's karate gear makes its first appearance since "Sandy's Nutmare."
- "Journey to the Center of Karen" is a pun on Journey to the Center of the Earth.