The Hammers go into the game feeling cursed after seeing six first team starters wiped out through injury in the last month.
Slaven Bilic's side are experiencing what seems to be an annual glut of injuries to key players after losing star man Dimitri Payet, strike duo Enner Valencia and Diafra Sakho, key playmaker Manuel Lanzini, winger Victor Moses and now leading defender Winston Reid.
There has been speculation Valencia could return to the bench for the Irons against Stoke tomorrow, a full month sooner than expected but that has not been confirmed by the club.
It means Bilic could left in the unenviable position of relying on injury-prone striker Andy Carroll and the unfancied Nikica Jelavic up front.
To complicate matters West Ham welcome a Stoke side who have been winning plaudits for their recent performances winning 2-0 against Manchester City last time out in a game they could have won even more comfortably.
The East Londoners were already with Payet, Lanzni and Sakho when they earned a draw at Old Trafford last time out.
But who should replace the likes of Moses and Reid and how will the Hammers alter their starting XI to accommodate them?
Jenkinson in for Reid
Carl Jenkinson was dropped to the bench for West Ham's trip to Manchester United as Bilic reverted to the back four which has served him so well on the road in wins over the likes of Arsenal, Liverpool and Manchester City this season.
Shifting James Tomkins to right back West Ham look a lot more solid but lose Jenkinson's attacking threat and pace.
With Reid out, though, Tomkins should move back into the centre of defence with Arsenal loanee Jenkinson restored to right back as his pace will be crucial against the likes of Marko Arnautovic.
James Collins will be the back-up on the bench.
Antonio in for Moses
Michail Antonio, a £7million signing from Nottingham Forest in the summer, has barely featured under new Hammers boss Bilic.
But the powerful winger has finally been given a chance as a result of West Ham's crippling injury list, impressing after replacing Moses in the 0-0 draw at Manchester United last time out.
He has to make his first start against Stoke to inject some much needed pace into the Hammers midfield.
Of course Bilic could elect to bring in Collins alongside Angelo Ogbonna at the back, leave Tomkins at right back and play Jenkinson as a winger, the role he filled as a sub at Old Trafford.
With him and Antonio on opposite flanks the Irons would have plenty of pace out wide.
Mauro Zarate played well last time out even if his finishing did let him down and Nikica Jelavic will have to wait a little while more for his first start.