Rodrigo Bentancur's season is over, adding injury to the insult of Saturday's shambolic 4-1 defeat by Leicester on one of the worst days of Antonio Conte's tenure.
The Uruguay midfielder is expected to be sidelined for six to seven months after suffering an ACL tear, robbing Conte of a player who transformed his side in the second half of last season and lessening the chances of a repeat this term.
Bentancur has added poise, tenacity, energy and goals to Spurs, and his ability to resist the opposition press and lead transitions is key to Conte's approach.
Spurs have already endured a brief taste of life without the 25-year-old when he was ruled out for five matches with an injury picked up at the World Cup, and it was not pretty, including defeats by Aston Villa and Arsenal.
In different circumstances, his injury would have been an opportunity for Yves Bissouma but, cruelly, the summer signing is also facing an extended spell on the sidelines following ankle surgery on Friday, leaving Conte relying on Oliver Skipp, 22, and 20-year-old Pape Matar Sarr.
The head coach's reluctance to rotate also means the young pair are coming in cold. Skipp (right) has started just five games this season and Sarr has one Spurs start.
To make matters even worse in the immediate term, Pierre-Emile Hojbjerg is suspended for tomorrow's Champions League last-16 first leg against AC Milan in what is likely to be the last rest afforded to the Denmark midfielder before the end of the season.
Eric Dier could step into midfield at the San Siro but that would rob Conte of a key component of his three-man defence.
Ivan Perisic is experienced and versatile enough to play anywhere but is the only available left wing-back after Ryan Sessegnon succumbed to a hamstring injury, which is expected to rule him out for six weeks.
Tottenham's mounting injury list, also including captain Hugo Lloris, will test Conte's ability to adapt to circumstances after a dismal performance at the King Power Stadium, prompting an all-too-familiar question: is the head coach underperforming or are his players not good enough?
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From the moment Nampalys Mendy cancelled out Bentancur's opener, Spurs' makeshift back-line was all at sea and the scoreline ultimately flattered the visitors.
In the absence of Lloris and the suspended Cristian Romero, Conte started with a back four of Fraser Forster, Japhet Tanganga, Dier and Ben Davies.
The same personnel were short of the required standard back when Jose Mourinho was in charge (for Forster, read Joe Hart), and yet several transfer windows later, Conte is still faced with having to use them in the Premier League — a damning indictment of the club's recruitment.
Conte approach, which has been a success at all his previous clubs, relies on top-level centre-backs, and yet the only recruit in that area in three transfer windows under the Italian is loanee Clement Lenglet.
There is plainly no point in having a coach like Conte if the club do not give him the tools to be a success.
That said, Dier and Davies are both experienced internationals but they looked desperately under-coached against Leicester, with the goals by James Maddison, Kelechi Iheanacho and Harvey Barnes all soft.
Only five teams have conceded more than Spurs' 35 in 23 League games, including Leicester, and Conte should at least be able to organise a defence and get the best out of every player, even if they are not of the standard he is used to.
There is also a compelling argument that Conte should stop persisting with a system that relies so heavily on defending until he can call on top-level defenders, with the coach currently failing to play to the obvious strengths of his top-heavy squad.
In the absence of World Cup finalists Lloris and Romero, Spurs were always going to struggle to match the magnificent rearguard they produced in the 1-0 win over Manchester City but Conte persisted with using three centre-backs at Leicester, regardless.
Why start Tanganga, for example, when he could have switched to 4-2-3-1 and played Brazil's No.9 Richarlison alongside Harry Kane against one of the few defences in the League that is even more porous than his own?
Unless Skipp or Sarr (left)can step up, Bentancur's injury will make it even harder for Conte to make a success of his rigid approach, and if ever there was a time for the head coach to get creative, it is now.
Plainly, Conte is still reliant on too many players who should have been upgraded on before now, which is not his fault, but he shares responsibility for Spurs's stuttering season and must adapt to the loss of key men.