Cruz, who will miss the rest of the regular season for the playoff-contending Rangers, was among 13 players disciplined Monday for their relationship to Biogenesis of America, a closed anti-aging clinic in Florida accused of distributing banned performing-enhancing drugs.
The All-Star right fielder said he had a gastrointestinal infection from November 2011 through January 2012 that wasn't properly diagnosed at first.
"By time I was properly diagnosed and treated, I had lost 40 pounds. Just weeks before I was to report to spring training in 2012, I was unsure whether I would be physically able to play," Cruz said. "Faced with this situation, I made an error in judgment that I deeply regret, and I accept full responsibility for that error. I should have handled the situation differently, and my illness was no excuse."
He provided no other specifics.
That was around the same time the Rangers were fresh off their second consecutive World Series appearance, and Cruz signed a $16 million, two-year contract to avoid salary arbitration. He was MVP of the 2011 AL championship series.
Cruz, eligible for free agency after this season, is batting .269 with a team-high 27 home runs and 76 RBIs in 108 games this season.
"It goes without saying we're not going to replace Nelson's production with any one player, whether that's internally or via a trade," Texas general manager Jon Daniels said on a conference call. "We're going to be creative"
Daniels also reiterated a statement issued earlier by the team expressing its disappointment in Cruz for violating MLB's drug policy and its full support of "efforts to eliminate performance-enhancing substances from our game."
The 50-game suspension corresponds with the last 50 games of the regular season for Texas, which has been the playoffs the last three seasons.
The penalty will cost Cruz $2,732,240 in salary for the rest of this season and the possibility of earning another $500,000 in potential performance bonuses based on plate appearances that are no longer attainable.
Texas had won six of seven before Monday night's game at the Los Angeles Angels, trimming its deficit behind AL West-leading Oakland from six games to 2 1/2 games. Cruz hit three homers in those seven games, including one in Sunday's 4-0 victory against the Athletics in the rubber game of the weekend series.
Cruz, who turned 33 last month, would be eligible for the playoffs if the Rangers make the postseason.
Daniels said the team would be "open-minded" to Cruz's return for the playoffs, but wanted to see how the situation plays out in the coming weeks.
"Assuming that there's no other information that we're not yet aware of and if his teammates welcome him back, and Nellie handles this well, which I expect he probably will, then we're open to it," Daniels said.
Before their series opener at the Los Angeles Angels, Rangers teammates expressed their support for Cruz.
"It's upsetting a little bit. He's a great teammate and he's been a big part of this ballclub for a lot of years. It's going to be a little bit tough not having him around," center fielder Craig Gentry said. "But I didn't lose any respect for him. He's a great teammate. We know where his heart is."
The non-waiver trade deadline passed last week without the Rangers adding a right-handed hitter that could potentially help fill the void without Cruz.
The Rangers recalled outfielder Engel Beltre from Triple-A Round Rock and selected the contract of outfielder Joey Butler from the same team. They also designated infielder Adam Rosales for assignment, three days after adding him on a waiver claim from Oakland.
Cruz had never been linked to performance-ending drugs before he was among the players targeted by MLB in a scandal that started last January with a Miami New Times story about Biogenesis.
After his name showed up in that report, attorneys for Cruz issued a statement denying the allegations. When Cruz arrived at spring training in February he said it was "shocking" and "depressing" to have his name connected with Biogenesis.
In his statement Monday, Cruz expressed thanks "for the unwavering support of my family, friends, and teammates during this difficult time. I look forward to regaining the trust and respect of the Rangers organization, my teammates, and the great Rangers' fans, and I am grateful for the opportunity to rejoin the team for the playoffs."
Even with lingering questions hanging over his head, Cruz became an All-Star for the second time as one of the top hitters for the Rangers, who needed his production after the departures of free agents Josh Hamilton and Mike Napoli last winter.
Cruz was originally acquired in a six-player trade at the non-waiver deadline in July 2006, when he came with Carlos Lee from Milwaukee. His first full major league season was 2009, when he was an All-Star and hit a career-high 33 homers.
In 34 career playoff games over the last three years, Cruz is batting .278 with 14 homers and 27 RBIs.
That includes the six-game ALCS against Detroit in 2011, when Cruz had six home runs and 13 RBIs, both major league records for a postseason series. He had the first game-ending grand slam in postseason history, and was the first player with extra-inning homers in two games of one series.
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