The Hammers wideman was forced off after just eight minutes of Tuesday's second-round Carabao Cup win - and the early signs are not good.
The former Nottingham Forest man immediately knew he was unable to continue in the cup clash and, even though boss Manuel Pellegrini initially suggested in the aftermath of the game that he's facing "a couple of weeks" out, there are real fears he may be on the sidelines for a significantly longer period.
Speaking after the 2-0 win, Pellegrini said: "It was a hamstring injury and we see how big it is tomorrow, but probably he will not be available for a couple of weeks.
"We have the international break after the game on Saturday so after 15 days we will see how big the injury is and we will know how long he is out for."
Despite Pellegrini's apparent optimism, there are plenty of reports suggesting the winger has sustained a serious hamstring tear that may even need an operation - and that could mean up to three months out, or possibly even longer.
It is being claimed the severity of the strain will be assessed in the next few days but he cannot even undergo a scan yet due to swelling, which is another bad sign that the setback is a much more serious one.
The Hammers are expected to update fans later in the week on the extent of the injury and it could be that come Friday, Antonio's prognosis is not as bleak as feared, but it's just the latest worrying development in his Hammers career, that has been punctuated by injury problems.
The 29-year-old has already had one operation on his other leg after suffering a hamstring injury in the second half of the 2017-18 campaign - a setback that kept him out for four months - and there are worries the same situation could arise again.
Antonio has been with West Ham since 2015 and has made 132 appearances in all competitions, scoring 28 goals in that time.
He will definitely miss this weekend's home game in the Premier League against Norwich City and had featured in all three league games so far this season, starting once.
In Antonio's absence, the likes of Jack Wilshere and Carlos Sanchez will hope for more first-team opportunities in Pellegrini's side.