The Senegal international leads Tottenham ace Toby Alderweireld in the market, having been a long-term target for the Red Devils.
Jose Mourinho bemoaned his lack of quality in defence once again following their humbling defeat to Juventus.
And now Betfair have Koulibaly at 6/1 to move to Old Trafford in January.
The Special One was not backed to buy a leading centre back in the summer and has since criticised the state of his squad in a number of public outbursts.
Alderweireld is priced at 9/1 for the switch which is the same price as Bayern Munich ace Jerome Boateng.
Betfair: Top five most-likely defenders to sign for United in January
Betfair Spokesperson Katie Baylis said: “United's defence this year has been a massive issue and while they only conceded one goal last night against Juventus, it is an issue that won’t go away and will be surely one of the big factors in the next transfer window.
"We have Koulibaly at 6/1, Alderweireld and Boateng at 9/1, Gimenez at 10/1 and Varane at 16/1 as likely targets for United.
"This list could grow if their defensive woes continue to rumble on.”
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