The 23-year-old has not featured for United since their Carabao Cup defeat against Brighton on September 16, when he was substituted in the 66th minute.
The striker has undergone multiple examinations as the club attempts to establish the precise nature of the problem. The latest information indicates that the current issue is an impact injury rather than shin splints, although it follows a period of recurring discomfort in the same area.
Sesko's absence is a significant setback for head coach Michael Carrick, who has been deprived of his only orthodox centre-forward during a difficult period for the club.
The problem has affected the Slovenian since last season, when a shin complaint forced him to miss the final three Premier League matches after flaring up against Liverpool in May. He subsequently missed pre-season before returning to action at the beginning of the current campaign.
Sesko initially appeared to have put the issue behind him, scoring against Everton in the Premier League and Sabah FK in the Champions League. However, the setback against Brighton has left United searching for a solution to an injury that has proved difficult to resolve.
Since arriving from RB Leipzig in August 2025 in a deal worth £73.7 million, Sesko has made 38 appearances in all competitions, scoring 14 goals and providing one assist.
His contribution was particularly important in the Premier League last season, when he finished as United's joint-leading league goalscorer alongside Bryan Mbeumo with 11 goals, despite missing eight matches.
Manchester United will now have to manage a lengthy absence while attempting to improve their results. Sesko is expected to miss important league fixtures, including meetings with Liverpool and Arsenal, as well as at least three Champions League matches.
The situation could also influence United's plans for the January transfer window. The lack of a specialist striker has become an increasingly pressing concern, and the latest injury setback leaves Carrick with limited options in the central attacking position.
United's wider problems have been compounded by disappointing performances and growing scrutiny of the manager. The club are languishing in 16th place in the Premier League, with their last league victory coming against Ipswich on August 30.
They have also gone without a win in all competitions since September 10, while a 4-1 Champions League defeat against Como last week was followed by a 3-0 home loss to Bournemouth.
Captain Bruno Fernandes was an unused substitute against Bournemouth after criticising Carrick's tactics following the Como defeat. Reports subsequently indicated that the pair held talks on Tuesday in an attempt to resolve their differences.
Sesko's prolonged absence adds another complication for United as they attempt to arrest their slide. His return is not expected before January, leaving the club to find a way to generate goals without their recognised first-choice centre-forward.