Combatants who made their first appearance in comic books.
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- Sally Acorn
- Sandman
- Saxton Hale
- Scarlet Witch
- Scott Pilgrim
- Scourge the Hedgehog
- Scrooge McDuck
- Sentinel
- Sentry
- Shadow the Hedgehog
- Shazam
- She-Hulk
- Shredder
- Silver Samurai
- Silver Surfer
- Skeletor
- Skye Prower
- Solomon Grundy
- Sonic the Hedgehog
- Spawn
- Spider-Gwen
- Spider-Ham
- Spider-Man
- Spider-Man 2099
- Star-Lord
- Starfire
- Static
- Steak
- Storm (X-Men)
- Super Fighting Robot (SCOTT PILGRIM)
- Superboy
- Supergirl
- Superman
- Superman (Injustice)
- Swamp Thing
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