The injury-prone defender was hoping to avoid a second groin operation of the year in order to play some part in Spurs' remaining games but it now appears Harry Redknapp will have to make do without another defender.
The latest injury means that Redknapp will only have Michael Dawson and Sebastien Bassong available at centre-back for Tuesday night's Champions League showdown with Real Madrid.
Injured again: Ledley King has only played seven times this season
'We have lost Ledley King, it looks like he will have to have an operation that will finish his season, said Redknapp.
'He has had problems with his knee for a long time, but that doesn't seem too bad - it's just his groin.'
King - who had surgery on his troublesome groin only last month in Germany - joins Jonathan Woodgate (calf), Younes Kaboul and William Gallas (both knee) on the injury list.
Woodgate's career is reportedly in doubt after he limped out of a friendly with a Barnet XI with yet another injury, the 31-year-old has only played 277 games in a 14-season career.
Redknapp added: 'We started the year with six central defenders here. Now we have two.
'Jonathan Woodgate was making good progress but got a calf injury in a friendly against Barnet and Younes Kaboul is still out with a thigh strain.
'William Gallas has been for a scan on his knee today. He struggled at the weekend and we are now down to having just Michael Dawson and Sebastien Bassong.'
Career in doubt: Jonathan Woodgate has picked up a calf injury
King, 30, has also had a career blighted by injury - he has only featured 61 times for Spurs in the last four seasons.
The news will hit Redknapp even harder given that William Gallas has barely trained in the last two weeks since picking up a mystery knee problem in the 0-0 draw with West Ham.
The Frenchman, who recently signed a two-year contract, is having a scan on Thursday and Spurs fans will be praying for some good news on the defensive front.
Aaron Lennon has also recovered from the hamstring injury which kept him out of England's recent squad but Redknapp is still sweating over the fitness of Welsh wing wizard Gareth Bale.
Bale pulled out of Wales' clash with England, also with a hamstring injury, but Redknapp hopes he will fit to face Real Madrid.
'Gareth worked with the fitness coaches and he looked OK this morning,' Redknapp said.
'Whether he is OK to play two games this weekend is doubtful.
'We will have a look at that tomorrow and decide which way to go with it.
'Hopeful': Gareth Bale is a major doubt for the Wigan game but should be fit for Real Madrid
'We are going to leave it late. We'd love to have him fit but if he isn't fit then we can't play him.'
The Spurs boss is confident that his side will be able to give Real a good match in Spain even if Bale does not play next week.
'We have other good players here who can play on the left,' Redknapp said.
'Niko Kranjcar has just gone off and had a couple of games for Croatia. Steven Pienaar is fit now too.'
The positive news for Redknapp is thatTom Huddlestone is set to return against Wigan from a long-term ankleinjury and Aaron Lennon has recovered from the hamstring injury whichforced him to pull out of the squad.
Redknapp said: 'Aaron is OK. He trained this morning. There isn't any problem with him.
'He met up with England and stayed with them for 10 days, felt his hamstring was tight and we didn't want to risk him going so he pulled out of the squad.'
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Explore more:People: Sebastien Bassong, Jonathan Woodgate, William Gallas, Michael Dawson, Ledley King, Harry Redknapp, Younes Kaboul, Aaron Lennon, Gareth Bale, Niko Kranjcar Places: Germany, Spain, Croatia, United Kingdom, Wales