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- Michael O'Connor, P, Washington Nationals
- Darren O'Day, P, New York Mets
- Eric O'Flaherty, P, Atlanta Braves
- Sean O'Sullivan, P, Anaheim Angels
- Ivan Ochoa, SS, Boston Red Sox
- Jacob Odorizzi, P, Milwaukee Brewers
- Trent Oeltjen, RF, Arizona Diamondbacks
- Tomo Ohka, P, Cleveland Indians
- Ross Ohlendorf, P, Pittsburgh Pirates
- Will Ohman, P, Atlanta Braves
- Augie Ojeda, 2B, Arizona Diamondbacks
- Hideki Okajima, P, Boston Red Sox
- Darren Oliver, P, Anaheim Angels
- Miguel Olivo, C, Kansas City Royals
- Ray Olmedo, SS, Tampa Bay Rays
- Scott Olsen, P, Washington Nationals
- Garrett Olson, P, Seattle Mariners
- Magglio Ordonez, RF, Detroit Tigers
- Justin Orenduff, P, Los Angeles Dodgers
- Paulo Orlando, CF, Kansas City Royals
- Pete Orr, 2B, Washington Nationals
- Anthony Ortega, P, Anaheim Angels
- Adrian Ortiz, CF, Kansas City Royals
- David Ortiz, DH, Boston Red Sox
- Ramon Ortiz, P, San Francisco Giants
- Russ Ortiz, P, Houston Astros
- Dan Ortmeier, LF, Colorado Rockies
- Chad Orvella, P, Tampa Bay Rays
- Franquelis Osoria, P, Kansas City Royals
- Ian Ostlund, P, St. Louis Cardinals
- Roy Oswalt, P, Houston Astros
- Adam Ottavino, P, St. Louis Cardinals
- Joshua Outman, P, Oakland Athletics
- Lyle Overbay, 1B, Toronto Blue Jays
- Dylan Owen, P, New York Mets
- Henry Owens, P, Florida Marlins
- Jerry Owens, CF, Chicago White Sox
- Micah Owings, P, Cincinnati Reds
- Pablo Ozuna, 2B, Philadelphia Phillies
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