The Spain international joined United on a temporary basis in the summer following injuries to Luke Shaw and Tyrell Malacia.
With both players now closing in on their returns, United have seen fit to send the 27-year-old back to his parent club Tottenham.
A statement on United’s official website read: ‘Sergio Reguilon is returning to his parent club Tottenham Hotspur after Manchester United activated a break clause in the loan agreement.
‘The Spanish left-back joined on a temporary basis last August and made a positive contribution during the first half of the season.
‘Sergio fulfilled the role he was brought in for: to provide cover for Luke Shaw and Tyrell Malacia while both were out with long-term injuries.
‘While Luke has missed the past two games with a minor injury, the England international is expected back soon. Tyrell, meanwhile, is getting closer to a return from his knee injury.
‘The versatile Diogo Dalot can also provide further cover at left-back.
‘With fewer games in the second half of the season and injured players returning, there will be less opportunity for Sergio to play. It was decided it was in the best interests of all parties for Reguilon to return to Spurs.
‘The 27-year-old defender leaves United with our appreciation for his contribution and best wishes for the future.’
United, meanwhile, face Wigan in the FA Cup third round this weekend and have been boosted by the return to training of first team stars Lisandro Martinez and Casemiro, following lengthy absences.
Goalkeeper Andre Onana, meanwhile, has been granted permission to delay joining up with the Cameroon squad ahead of the Africa Cup of Nations.
Onana will, therefore, be available to play against the Latics and Tottenham in the Premier League, meaning his fellow summer signing Altay Bayindir will have to wait to make his long awaited debut.