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- Michael O'Connor, P, Washington Nationals
- Darren O'Day, P, Anaheim Angels
- Eric O'Flaherty, P, Seattle Mariners
- Sean O'Sullivan, P, Anaheim Angels
- Wes Obermueller, P, Florida Marlins
- Ivan Ochoa, SS, San Francisco Giants
- Tomo Ohka, P, Chicago White Sox
- Ross Ohlendorf, P, New York Yankees
- Will Ohman, P, Atlanta Braves
- Augie Ojeda, SS, Arizona Diamondbacks
- Hideki Okajima, P, Boston Red Sox
- Darren Oliver, P, Anaheim Angels
- Miguel Olivo, C, Kansas City Royals
- Ray Olmedo, SS, Philadelphia Phillies
- Scott Olsen, P, Florida Marlins
- Garrett Olson, P, Baltimore Orioles
- Brian Omogrosso, P, Chicago White Sox
- Magglio Ordonez, RF, Detroit Tigers
- Justin Orenduff, P, Los Angeles Dodgers
- Pete Orr, DH, Atlanta Braves
- Anthony Ortega, P, Anaheim Angels
- David Ortiz, DH, Boston Red Sox
- Ramon Ortiz, P, Colorado Rockies
- Russ Ortiz, P, San Francisco Giants
- Dan Ortmeier, RF, San Francisco Giants
- Chad Orvella, P, Tampa Bay Rays
- Paul Oseguera, P, San Francisco Giants
- Franquelis Osoria, P, Pittsburgh Pirates
- Roy Oswalt, P, Houston Astros
- Akinori Otsuka, P, Texas Rangers
- Adam Ottavino, P, St. Louis Cardinals
- Joshua Outman, P, Philadelphia Phillies
- 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, Arizona Diamondbacks
- Pablo Ozuna, LF, Chicago White Sox
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