This week saw the return of European club competitions with Chelsea and Tottenham both involved.
More games means less recovery time and that could lead to fatigue and possibly injuries.
Then there are those who are still self isolating having tested positive to Covid-19 or might have travelled into red listed countries and are required to keep to themselves.
LondonWorld brings you a club by club injury update of all the Premier League teams in the City.
N’Golo Kante missed out on the Champions League victory against Zenit having picked up a hamstring injury just before the international break.
He trained twice this week and could be in line for a return against Tottenham on Sunday.
Christian Pulisicis still struggling with pain in his shin and the game against Tottenham might come too early for the American winger.
Son Heung-Min and Eric Dier missed the Europa Conference League game against Rennes but have all made progress and could play a part against Chelsea this weekend.
Steven Bergwijn and Lucas Moura picked up knocks against Rennes last night and are all in a race against time to be fit for this weekend.
The trio of Davinson Sanchez, Lo Celso and Cristian Romero will return to the UK on Saturday from their isolating camp in Croatia, less than 24 hours to the derby, but could still feature with Nuno Espirito Santo desperate to avoid back to back league defeats.
Defender Japhet Tanganga, sent off against Crystal Palace is unavailable.
Mohamed Elneny (hamstring) and Rob Holding (knee) are definitely out of the Burnley game.
Midfielder Granit Xhaka is back in London after catching Covid-19 on international break with Switzerland.
He has been training with the group but will serve the second of his three game suspension this weekend after being sent off against Manchester City.
There is some good news for manager Mikel Arteta who can call on midfielder Thomas Partey, the Ghanaian played only 28 minutes against Norwich and should be fit enough to start at Burnley this weekend.
West Ham United
David Moyes is going to be without top scorer Mikel Antonio who was sent off against Southampton.
He failed to sign a striker in the summer, it will be interesting to see how he sets up the team when Cristiano Ronaldo and his Manchester United team come to London this weekend.
The Hammers remain unbeaten this season but that will be put to test when United visit the London stadium.
Joshua Da Silva with a hip injury and Mads Sorensen knee are all long term and will not be involved against Wolverhampton Wanderers.
Frank Onyeka who tested positive for Covid-19 during the international break could only play 15 minutes against Brighton Hove and Albion.
He has trained fully this week and is in line for start.
Exciting English talent Eberechi Eze is still out with a long term injury and hard working left winger Jeffrey Schlupp is still struggling with the hamstring injury he picked up while on international duty with Ghana.
Palace will be buzzing after picking up an impressive victory against Tottenham last weekend, their first of the season.
Wilfred Zaha has trained all week and Conor Gallagher, on-loan from Chelsea appeared to be limping after Tottenham, but he is fit enough to start Liverpool.
Dan Gosling illness and Ben Foster thigh are all not ready for the game against Norwich.