Spurs have been missing Harry Kane since the turn of the year after he suffered a serious hamstring injury, and now they have been rocked by the news Son could also miss the rest of the season.
The South Korean forward has undergone surgery on a broken arm to leave Jose Mourinho with an even bigger headache heading into a crucial part of the season.
The timing could not be worse for Spurs given they are entering a possible season-defining period, with the two-legged Champions League tie with the Bundesliga side and games against top-four rivals Chelsea, Wolves and Manchester United in the next four weeks.
Mourinho has no out-and-out striker to call on, having declared academy prospect Troy Parrott not ready, meaning options are limited to playing Lucas Moura, Dele Alli or Steven Bergwijn.
The Spurs boss says they will battle on with what they have got and is hoping that Leipzig will underestimate his side, which could ultimately work in their favour.
"I'm not going to give up and probably opponents, they are thinking, 'Wow, now is the time to kill them,' " he said.
"I understand why they think that way but we are going to give everything and I don't think it's going to be easy for Leipzig to play against us. I don't think it will be easy for them."
Elsewhere, Erik Lamela will be assessed ahead of the game, but Son joins Kane, Moussa Sissoko and Juan Foyth on the injury list.
Leipzig do have one or two issues of their own heading into the clash as star central defender Dayot Upamecano is missing through suspension, while Ibrahima Konate and Willi Orban are both missing through injury.
Ethan Ampadu, who is on loan from Chelsea, could be handed a start at the Tottenham Hotspur Stadium.