The defeat was their seventh in the Premier League since Mourinho took charge, and they know that they can ill-afford any further setbacks if they are to bridge the gap to the Champions League places.
Here, Sports Mole looks at how Spurs could line up for Monday's contest.
One positive to come from the defeat to Sheffield United was that Spurs suffered no fresh injury concerns, but Dele Alli has since picked up an injury in training which leaves him as a doubt for this match.
Key players being missing was not the problem for Tottenham in the defeat, though, and the worry for Mourinho will be that the result came while his squad was almost at full strength.
Many of those players may start again on Monday, then, but the likes of Alli - if fit - and Toby Alderweireld will be hopeful of a recall - the latter especially so after some questionable Spurs defending for the Sheffield United goals.
The likes of Steven Bergwijn, Son Heung-min, Moussa Sissoko and Giovani Lo Celso could all start again, although Tanguy Ndombele, Jan Vertonghen and Harry Winks are among those waiting in the wings if Mourinho does choose to make changes.
Harry Kane will lead the line having scored against Sheffield United to complete his set of Premier League opponents, and he will be looking to continue an impressive record of nine goals in as many games against Everton.