Tate tested positive for a performance-enhancing substance that he said came from prescribed fertility medication. His appeal was heard Aug. 6 by an arbiter in New York.
The suspension will cost Tate $465,000 in salary ($116,176 per game). He will miss the opener on the road against the Dallas Cowboys followed by games against the Buffalo Bills, Tampa Bay Buccaneers and Washington Redskins.
He will be allowed to participate in all preseason practices and games.
"This morning, I received the unfortunate news that my appeal was denied," Tate said in a statement Tuesday. "I went into this arbitration with the understanding that due to the facts, unlike many other cases, we could be the exception to win. Unfortunately the NFL stood by their no tolerance policy, which I hope one day to help have a part in reforming, so no other player has to go through this situation."
The NFL and NFLPA have Therapeutic Use Exemptions (TUEs) available to players who need to take medications that are appropriate for the treatment of specific medical conditions. The exemptions include fertility issues since some fertility drugs are known to serve as masking agents. However, players must submit an application filled out by their physician to receive approval for a TUE.
Tate did not follow that protocol, and therefore was "referred for administrative action" under the league's policy for PEDs.
"No one is more upset than myself, but moving forward, all I can do is continue to be a leader, continue to hold myself to the highest character and integrity, and soon make the biggest impact on the field," Tate said in his statement.
Tate's absence will put added pressure on a wide receiver corps that lost Odell Beckham Jr. in an offseason trade. Tate signed a four-year, $37.5 million deal as a free agent to help offset the loss.
Latimer is expected to slide into Tate's starting spot. He started in Thursday's preseason opener with Shepard still sidelined and caught two passes for 36 yards despite playing just two drives.
On Tuesday, before the decision was announced, Giants quarterback Eli Manning lauded Tate's ability and said he hoped "things work out" for the receiver to play a full season.
"Golden is a smart player and he is going to be in the right spot and he has a good feel for the zones, how to get open versus different techniques and stuff," Manning said. "A veteran guy but also, we have seen a bunch of it with the Giants, his run after catch historically has been very good -- a playmaker. Hopefully, things work out and he will be here all year."
In a statement last month, Tate said he thought he had a legitimate case to win his appeal.
However, the NFL's policy on performance-enhancing drugs is unforgiving. It states, "Players are responsible for what is in their bodies and a positive test will not be excused because a Player was unaware that he was taking a Prohibited Substance."