In trimming their squad to 19 for the game 24 hours before Saturday's 5:30pm (AEST) kick-off, McCullough was the key name missing for the Red V.
A brief statement from the Dragons accompanying their team list confirmed the veteran rake - who has played 297 NRL games, has suffered a thumb injury.
There was no mention of the severity of the injury, or whether he is likely to miss more than just the upcoming game against the Titans, with the Dragons to take on the New Zealand Warriors and Canterbury Bulldogs in the coming weeks before a Round 13 bye ahead of the opening State of Origin clash on June 8.
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In his place, the Dragons have promoted young gun Jayden Sullivan to play at dummy half out of position.
Hooker is a position the Dragons are incredibly short in with no other recognised hooker outside of McCullough in their top 30, and while Sullivan did an admirable job filling in for the Red V last year when the club battled injuries to McCullough and others, the prospect of him playing 80 minutes out of position is a concern for the club.
George Burgess has also dropped out of the squad, with Jack Gosiewski joining the bench, however, none of Blake Lawrie, Aaron Woods, Tyrell Fuimaono or Gosiewski will be able to fill in at dummy half for Sullivan to have a breather.
Kick-off is scheduled for 5:30pm (AEST) on Saturday evening at Suncorp Stadium in what will be the fourth game of magic round, leading into the huge Penrith Panthers and Melbourne Storm blockbuster to be played in front of a sold out crowd later that evening.