The final round of international fixtures in 2016 did no favors for managers of some of the English Premier League's title hopefuls.
Jose Mourinho and Arsene Wenger, in particular, will vouch for that ahead of the renewal of their often-heated coaching rivalry.
When Mourinho's Manchester United and Wenger's Arsenal meet at Old Trafford on Saturday for the standout game in the 12th round of matches, there could be some major names missing because of injuries sustained on international duty.
United captain Wayne Rooney has caused a furor by being photographed, looking bleary-eyed, alongside some guests at a wedding party taking place at the England team hotel on Saturday. But by then, he'd picked up a knee injury during England's 3-0 win over Scotland the night before, causing him to miss Tuesday's match against Spain, and Rooney is now doubtful for the Arsenal game.
It was the last thing Mourinho would have wanted, considering he is already without suspended striker Zlatan Ibrahimovic and center backs Eric Bailly and Chris Smalling, as well as having serious doubts over the fitness of midfielder Marouane Fellaini and full backs Luke Shaw and Antonio Valencia.
Wenger, meanwhile, will ask Alexis Sanchez for an honest assessment of his fitness after Arsenal's star forward sustained a hamstring injury while away with Chile. Sanchez missed a draw against Colombia but returned for the 3-1 win over Uruguay on Tuesday, although his right leg was heavily strapped for the match.
Sanchez isn't due to return to Arsenal's training base until Friday and the match against United is a lunchtime kickoff on Saturday.
"What I will consider is the risk of injury because he played while recovering from a hamstring injury," Wenger said on Thursday. "I'll consider the way he feels as well. On that front you depend on the honesty of the player, how they feel and how they recover."
Wenger will be careful about overloading Sanchez, who has scored eight goals for Arsenal this season from his new position as converted striker. This time last year, Sanchez picked up a hamstring injury following a grueling run of back-to-back games for club and country and ended up missing the next two months, which proved to be a huge blow to Arsenal's title hopes.
Arsenal plays Paris Saint-Germain in a big Champions League game on Wednesday, too.
Liverpool and Chelsea, the Premier League's top two, could also be counting the cost of the recent international games after injuries to key players.
Adam Lallana, one of Liverpool's quartet of sprightly forwards that has been in devastating form this season, hobbled off during England's game against Spain and is a doubt for the leaders' trip to Southampton.
As for second-place Chelsea, Diego Costa was ruled out of both of Spain's games during the break because of groin injury and Eden Hazard limped off during Belgium's 8-1 win over Estonia with an apparent calf injury. It isn't yet clear if either Costa or Hazard — the scorers of 15 league goals between them — will be fit for the Chelsea's match at Middlesbrough.
Here's what else to look out for this weekend:
CRYSTAL PALACE-MANCHESTER CITY
Palace has conceded 10 goals in its last three games and hasn't kept a clean sheet in the league all season. In terms of points per game (0.73) in 2016, Alan Pardew's side is the worst-performing team across England's four leagues this calendar year.
Probably, then, the last team it would want to see arriving at Selhurst Park on Saturday is Pep Guardiola's free-scoring Man City side. Star striker Sergio Aguero will be raring to go for City, having failed to start for Argentina in either of their World Cup qualifying games over the international break.
Leicester can clinch qualification to the knockout round of the Champions League on Tuesday, but its players would be wise not to look that far ahead this weekend.
The Premier League champions head to Watford just two points above the relegation zone, having lost at home to West Bromwich Albion in the last game before the international break.
Leicester will be boosted by leading striker Jamie Vardy ending his run of 14 games without a goal for club or country by scoring for England against Spain. Vardy scored 24 league goals last season, but has only two so far this season.