Squidward walks outside to find his yard covered in Gary's slime-trail. He attempts to keep Gary away by building a splintery wooden fence around him, but to no avail. As he complains to SpongeBob about this, Gary bites him. Squidward asks SpongeBob if Gary has had all of his shots, and he says that he has, until Patrick comes along and asks him if Gary has been vaccinated for "Mad Snail Disease", a disease that turns anyone bitten by the afflicted into a zombie, which SpongeBob says he has not. Suddenly, Gary runs off and starts to bite everybody in sight.
Bikini Bottom is sent into a state of mass hysteria and destruction, and soon, almost everybody has been bitten and turned into zombies. Those who have survived the disease are hiding out at the Krusty Krab. SpongeBob tries to get in, but they believe he is a zombie and will not let him in, until he slips through the doors. Old Man Jenkins suggests that they might all be zombies, and everyone starts panicking. Gary then comes in, much to the horror of the onlookers, and SpongeBob tries to bring him to his senses, but Gary bites him and he seemingly turns into a zombie too much to his sadness and horror. The survivors in the Krusty Krab decide to terminate Gary.
However, a doctor named Gill Gilliam enters the building to put an end to the commotion, explaining that the disease is just an urban legend and that the supposed symptoms were all in their imaginations, and that Gary was simply suffering from "Grouchy Snailitis" due to a "tiny" splinter in his foot from Squidward's fence, which he removes. SpongeBob is happy that Gary was never disease-ridden and asks if he still loves him with Gary meowing in response. The remaining people outside appear to hear this and even though they are not infected, Squidward still acts like a zombie due to the fact that he is now working at his job. The episode ends with Gary biting Mr. Krabs.
Mad snail disease is a reference to mad cow disease, aka bovine spongiform encephalopathy (BSE). Ironically, mad snail disease is more similar to rabies than it is to mad cow disease. See List of Fictional Diseases.
If one will think very carefully, the cause of everything in this episode is because SpongeBob allows Gary into Squidward's house and also because Squidward made the poles. He could just used the shocking cage like he used in "Breath of Fresh Squidward."
Once Bitten is based on the phrase, "Once Bitten, Twice Shy," which means if someone is hurt by someone or something before, they will be more cautious next time.
The second part of this episode where the fishes turn into "zombies" is a parody of the George Romero movie "Night Of The Living Dead."
During the news report with Perch Perkins, a fish states: "it is spreading through the air," this is impossible because they are underwater.
Nat is seen as a zombie but later, he is in the Krusty Krab.
When SpongeBob arrived at the Krusty Krab, the doors were locked. Later on when Squidward walks in acting as a zombie, the doors were unlocked (no one was seen unlocking the door but it is possible Squidward had a spare set of krusty krab keys and unlocked it off screen).
During the scene where SpongeBob says to Gary, "I knew you weren't disease-ridden!," Frank's purple shirt sleeve turned blue. In the next scene, it changes back to purple.