Tottenham were left to rue their terrible luck with Steven Bergwijn and Lucas Moura both doubtful for their Premier League game against Chelsea.
The pair picked up injuries during Thursday's 2-2 Europa Conference League draw against Rennes.
Dutch winger Bergwijn limped out of the match on the half-hour mark and was soon followed by Brazilian Moura, adding to Spurs growing injury list with Son Heung-min already battling a calf issue.
Manager Nuno Espirito Santo is now looking short of options for Sunday's Premier League clash with Chelsea.
That is in addition to having Cristian Romero, Giovani Lo Celso and Davinson Sanchez unavailable in all likelihood as they quarantine in Croatia after they defied Premier League rules to travel to South America for international duty a fortnight ago.
Defenders Eric Dier and Ryan Sessegnon on the treatment table, while defender Japhet Tanganga is unavailable due to suspension.
"It feels painful, it feels really bad," Nuno said. "They are being taken care of by the medical department, but it's been tough."
"It's been terrible. I must be honest. Let's not hide behind anything," he said. "After the Watford game, everything that has happened has not been very good for us.
"But this is football. And we know it's a moment we have to overcome."
Spurs are seventh in the Premier League after suffering their first defeat of the season at Crystal Palace last weekend.
Second-placed Chelsea are behind United only on goals scored and will look to extend their unbeaten start in the London derby.
Chelsea striker Romelu Lukaku will go head to head with Tottenham's Harry Kane in a shoot-out between two of the Premier League's leading marksmen.
Lukaku has made a flying start on his return to Chelsea following his club record £98 million ($135 million) move from Inter Milan.