The centre-back pulled out of the warm-up against Aston Villa on Sunday with an adductor issue and was replaced in the starting line-up by Kevin Danso, as he is again here.
Although Thomas Frank insisted it was not a serious problem, Romero did not train with the Spurs squad on Tuesday and has not travelled for his side's latest Champions League test.
"It's an adductor strain,” Frank said at his pre-match press conference. “We will assess it more this week before we confirm any timeframe."
Destiny Udogie will also miss the match and he has been replaced by Archie Gray in the back four, with Djed Spence, the natural replacement, dropping to the bench.
”The latest is that he got that knee irritation after international duty,” the Spurs boss said.
“We are assessing and working very hard to get on top of it. We'll know more day by day."
Mathys Tel has led the line in the last two matches, but he is not in Spurs' squad for the league phase of the Champions League and so Richarlison returns to the starting line-up.