Manchester United are likely to be without Antonio Valencia, Sergio Romero and Marcos Rojo for the derby against Manchester City at Old Trafford on 10 September due to their late arrival back from international duty. The trio will all participate in South American World Cup qualifying over the next fortnight, meaning they will not return to English shores until less than 24 hours before the meeting with Pep Guardiola's side.
While Valencia will represent Ecuador in fixtures against Brazil and Peru, Romero and Rojo have been called up for Argentina's qualifiers against Uruguay and Venezuela. They are among 16 United players taking part in international games but none face as gruelling a schedule ahead of the biggest match of the season so far.
Each player faces a 5,000 mile plus journey on the eve of the game, meaning they are unlikely to be involved in Jose Mourinho's plans for his first derby in charge of United. The Portuguese coach has benefited from a fully fit squad during his first four competitive matches in charge but the rigours of the international schedule are set to bite.
"We keep eight outfield players and Sam Johnstone as the goalkeeper [for training]," he told United's official website. "We are going to lose the others and we don't know the way they train, the way they recover, the life they are going to have with their national teams. Some are coming back on the Monday before the Manchester City match but some are coming back on Friday.
"The day before Man City, we will still have Sergio Romero, Marcos Rojo and Antonio Valencia arriving. It will be a complicated process but we know it is like this when we have these players. And I would love all of the players to go because it would mean that everybody is being selected for their national teams."
Valencia has played every minute of United's season under Mourinho at right-back, while goalkeeper Romero has been an unused substitute in each of their four games as understudy to David de Gea. Rojo, meanwhile, played 21 minutes of the Community Shield win over Leicester City but has not been involved in a matchday squad since the opening day Premier League win over Bournemouth.
Meanwhile, Mourinho could yet be without a fourth player for the Manchester derby after new signing Henrikh Mkhitaryan went off injured during Armenia's 3-0 friendly loss to the Czech Republic. The 27-year-old was withdrawn with a knee problem in the 38th minute, following a collision with opposition defender Marek Suchy, but there is yet no indication whether he will be forced to pull out of the squad for the World Cup qualifier against Denmark on Sunday (4 September).