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The Mutants are barbarians from the planet Plun-Darr who constantly wage war against the ThunderCats both on Thundera and Third Earth. They are divided into several varied species, and though many exist, most episodes deal with just Slithe, Jackalman, Monkian and Vultureman.
Shortly after arriving on Third Earth, the Mutants formed a partial-alliance with Mumm-Ra to serve him and destroy the ThunderCats while also being spared his wrath for coming to "his" planet. After establishing an outpost for themselves, the Mutants enslaved a race of beings known as Brutemen in order to construct Castle Plun-Darr and terrorize natives of Third Earth to plunder their resources, wreak havoc, and provoke the ThunderCats. However, the ThunderCats prove to be formidable adversaries and the Mutants soon revisit Mumm-Ra to request he raise their spaceship from the desert for salvage purposes to help them compete with ThunderCat technology. This enables Vultureman to develop several vehicles for the Mutants: the NoseDiver, the SkyCutters, the Flying Machine, and the Fistpounder. Despite this, they continue to be thwarted by the ThunderCats at every turn, with the only thing Mutants are ever able to get away with being petty crimes like stealing "munchies" from the local crops. However they can still prove to be formidable foes on rare occasions and a threat to locals, but by the time the Lunataks arrive, the Mutants have become almost inactive, preferring to hide away in their fortress playing cards and eating stolen food all day. Eventually though, the threat of the Mutants would finally be dealt with after the arrival of Captain Bragg who took all the remaining Mutants away to Way Outback.
Mutant varieties include: Reptilians, Monkians, Jackalmen, Vulturemen, and Ratmen. After the destruction of Plun-Darr and Thundera, Mutants became few in numbers but still had more numbers than the ThunderCats on Third Earth. However the fate of Vulturemen and Ratmen is unknown as Vultureman and Ratar-O are the only members of their tribes ever seen. Ratar-O apparently operates outside Third Earth, but it is unknown if any other Mutants survived alongside him or if he and the ones on Third Earth are the last of their kind.
Female Mutants are also never seen and none of them are seen or mentioned among the Mutant survivors of Third Earth. In Trouble with Time, Slithe even acknowledges how the absence of females have negatively affected the day-to-day lives of Mutants. The only female Mutant ever mentioned was "Merna" who was just part of a ruse created by Captain Bragg to trap the Mutants, but its quite clear the Mutants leaders were desperate to meet her, showing that even by the end of the series they had still not found any female Mutants.
- Slithe - leader of the Mutants; opportunistic, cunning, and skeptical. Originally a lowly army cook who used to serve under Ratar-O back on Plun-Darr, but took on the role of leader after Plun-Darr's destruction.
- Jackalman - assistant Mutant to Slithe.
- Monkian - assistant Mutant to Slithe; his ability to quickly navigate the jungles helps Mutant espionage. Is also good source of intel on the ThunderCats thanks to his anonymous female source.
- Vultureman - inventor, mechanic, chemist; he provides the Mutants with technological support; he's not as core to the group as the other three but he's a regularly recurring character with his own quarters in Castle Plun-Darr.
- Ratar-O - domineering Mutant commander; captain of the Ratstar, a Mutant spaceship. Is actually Slithe's superior.
- Ratilla - Ratar-O's ancestor, wielder of the powerful Sword of Plun-Darr and presumably a Mutant of the highest order.
- Mutant Mothership - the Mutant spaceship; salvaged to create other vehicles/technology.
- NoseDiver - a hovercraft with amphibious capabilities; the favored vehicle of Slithe.
- SkyCutters - light aircraft used by the Mutants.
- Flying Machine - large aircraft; Vultureman's favored vehicle.
- Ratstar - Ratar-O's spaceship; it crashes and is salvaged for various parts but later is restored.
- Mutank - a ground vehicle created from salvaged Ratstar parts.
- Fistpounder - a heavy ground vehicle created to oppose the ThunderTank; Monkian debuts this vehicle.
- Early on, many mutants were shown to have been alongside Slithe when he first landed on Third Earth, however he would rarely use them to help combat the ThunderCats despite the larger numbers, preferring only the assistance of Monkian and Jackalman while regulating the others to guard duty, cooking and castle maintenance. Although one possible reason for this was that many Mutants, like the Reptilian and Jackal guards were shown to be very lazy and tremendous cowards, likely not making them very effective.
- Eventually these nameless mutant guards would stop appearing altogether after The Trouble with ThunderKittens and they were not seen being taken away by Captain Bragg in The Circus Train. So their exact fate is unknown, although its possible the writers forgot about them after season 1 due to the change in writing, as with most continuity errors that occurred after season 1.
- Vultureman is never seen with the Mutants when they first land on Third Earth, and does not appear until 13 episodes later. Whether he was simply in hiding or arrived on Third Earth at a later time than the other Mutants remains unknown.