Sheffield United midfielder Jose Baxter and Wolverhampton goalkeeper Aaron McCarey have both failed drugs tests and been placed under suspension, their clubs have announced.
A statement from Sheffield United on Saturday evening announced that "traces of a banned substance" were found when Baxter underwent Football Association testing.
Wolves said McCarey had failed a test for "a non-performance enhancing substance."
Both players protested their innocence, their clubs said.
An announcement on the Blades' official website said: "The club has learned that one of its players, Jose Baxter, was found to have traces of a banned substance in his sample following a routine Football Association out of competition drug test. The player has informed the club that he engaged in no wrongdoing involving any banned substance.
"Established policy in these circumstances requires that the club temporarily suspend the player pending further findings. The club has taken this step without prejudice to the player's claim of no wrongdoing. The club will offer no further comment at this stage."
Wolves said Republic of Ireland Under-21 international McCarey, who has not appeared for the Championship club in the league this season, "strenuously denies deliberately taking any banned substance."
Wolves' statement said: "Aaron McCarey has failed an out of competition Football Association drug test for a non-performance enhancing substance. As a result, the Wolves goalkeeper is now subject to an immediate FA suspension from all competitive forms of football. The immediate suspension is a standard procedure whilst the FA's investigation is concluded."
News of the failed tests comes a day after it was announced Hull midfielder Jake Livermore was suspended, reportedly also for failing a drugs test.
There was no official announcement of what examinations of Baxter's sample have shown up, though The Star reported that the substance in question was ecstasy.
Baxter, 23, rose through the Everton's ranks from the junior sides to the first team before finding opportunities were limited at Goodison Park. He moved on to Oldham in 2012, before joining United a year later.
An attack-minded player who can be pushed into the forward line, he scored 13 goals in the club's 2014-15 season, which ended in playoff semifinal defeat at the hands of Swindon.
The Professional Footballers' Association said it was providing support to Baxter.
A PFA statement read: "The PFA notes the charge levied against Jose Baxter of Sheffield United regarding an alleged anti-doping violation.
"We are providing our full support at this difficult time but will make no further comment as the matter is subject to the appropriate processes."
McCarey, 23, joined Wolves in 2010, but has failed to establish himself as a regular in the first team had has had loan spells with the likes of Walsall and York.