The Queensland State of Origin star was sin-binned and put on report for a high shot on fullback Jayden Campbell in the 21st minute of the Cowboys' 22-13 loss on Sunday.
Holmes will miss three games with an early guilty plea - that would enable him to return with two regular-season matches remaining - or four if he challenges it unsuccessfully.
Crucially it was the second time in consecutive weeks he had been binned for such an offence, Holmes also sat down for 10 minutes for a high shot on Mitchell Moses and copping a fine.
"I disagreed with his send-off last week but it is hard to disagree with tonight's call," Cowboys coach Todd Payten said after the game.
The Titans' win broke a four-game losing streak for the hosts and ended a six-match winning sequence for North Queensland.
Sitting eighth on 26 competition points, the Cowboys missed a golden chance to go fifth.
Brisbane forward Corey Jensen is a former North Queensland player and said he knew that Payten would have the side primed to cope with the loss of Holmes, should he be suspended.
He said he expected a "next man up" mentality at the Cowboys to ensure Holmes' replacement would do the job.
"He is a quality and an Origin player. He is a big out for them, but I know what their club is like and what Toddy is like," Jensen said.
"I have no doubt that if he is not there then the next person who comes in and plays will do the job for them."
With five rounds remaining, two competition points separate sixth-placed South Sydney, on 26 points, and Parramatta in 11th on 24.
Penrith centre Tyrone Peachey on Monday accepted a two-match ban for a careless high tackle on Cronulla forward Jack Williams.
Canterbury pair Jake Averillo and Reed Mahoney both escaped with fines for dangerous contact and shoulder charge citings respectively.
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