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- "Sandman" = Mariano Rivera, Panamanian closer
- "Sandy" = Sanford Brown Koufax, American starting pitcher
- "Satchel" = LeRoy Paige, American starting pitcher
- "The Say Hey Kid" = Willie Mays, American center fielder
- "Schnozz" = Ernie Lombardi, American catcher
- "Schoolboy" = Lynwood Rowe, American starting pitcher
- "Scooter" = Phil Rizzuto, American shortstop
- "Scrap Iron" = Phil Garner, American second baseman and third baseman
- "Seattle Bill" = Bill James, United States baseball player
- "The Secretary of Defense" = Garry Maddox, American center fielder
- "Señor October" = David Ortiz, Dominican DH
- "Señor Papi" = David Ortiz, Dominican DH
- "Señor Smoke" = Aurelio López, Mexican baseball player
- "The Shark" = Jeff Samardzija, American pitcher (and former college football player)
- "Shoeless" = Joe Jackson, United States baseball player
- "Shoeless Joe" = Joe Jackson, United States baseball player
- "Shotgun" = George Shuba, United States baseball player
- "Shrek" = Kevin Mench, United States baseball player
- "Silent George" = George Stone, American outfielder
- "The Silver Fox" = Edwin Snider, American center fielder
- "Skeeter" = James Webb, United States baseball player
- "Skoonj" = Carl Furillo, United States baseball player
- "Slammin' Sammy" = Sammy Sosa, Dominican right fielder
- "Smoke" = Dave Stewart, American starting pitcher
- "Smoky" = Forrest Harrill Burgess, United States baseball player
- "Snuffy" = George Stirnweiss, United States baseball player
- "Sockeye" = Tim Salmon, United States baseball player
- "Socks" = Ralph Seybold, United States baseball player
- "Soup" = Dave Campbell, American infielder, and announcer. Given the nickname due to the similarities to the famous soup company of the same name, and his last name.
- "The Spaceman" = Bill Lee, American starting pitcher
- "Spanky" = Mike LaValliere, American catcher
- "Sparkplug" = Johnny Damon, American outfielder
- "Sparky" =
- Albert Lyle, American closer
- Earl Adams, American second baseman
- George Anderson, American second baseman and manager
- "The Splendid Splinter" = Ted Williams, American left fielderr
- "The Springfield Rifle" = Vic Raschi, United States baseball player
- "Spuds" = Chris Sabo, United States baseball player
- "Stan the Man" = Stan Musial, American outfielder and first baseman
- "The Staten Island Scot" = Bobby Thomson, Scottish-born American outfielder
- "Steady Eddie" = Joseph Mayo, United States baseball player
- "Stretch" = Willie McCovey, American first baseman
- "Stuffy" = John McInniss, United States baseball player
- "The Sultan of Swat" = George Ruth, American starting pitcher and outfielder
- "Superjew" = Mike Epstein, United States baseball player
- "Superman" = Kevin Gregg, United States baseball player
- "Swede" = Charles Risberg, United States baseball player
- "Sweet Lou" =
- Lou Piniella, American outfielder and manager
- Lou Whitaker, American second baseman
- "Sweet Music" = Frank Viola, American starting pitcher
- "Sweet Swingin' Billy" = Billy Williams, American outfielder
Read more about this topic: List Of Baseball Player Nicknames