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The 26-year-old pulled out of the recent England double-header with a thigh strain and also sat out Saturday's Premier League win at Everton.
However, Sir Alex Ferguson was optimistic Hargreaves would be fit for the trip to Portugal, when United begin their quest to do better then last season's semi-final appearance.
But Hargreaves was unable to train on Monday morning and now appears resigned to setting his sights on the weekend game with Chelsea instead.
"It's okay, I have never really had this injury before so this is new territory," said the midfielder.
"I thought I would be fit for the Israel game, then the Russia game and then Everton, but I've still not done it. I have to take it day by day so hopefully I will be fit for the weekend.
"I can't say for certain but it looks as though I won't be ready for Wednesday because I have not trained."
Hargreaves believes this latest injury, allied to the tendinitis problem which effectively scuppered his pre-season programme and ruled him out of the Red Devils' opening two games against Reading and Portsmouth, is a legacy of the broken leg he suffered in Germany 12 months ago.
"It is frustrating," he said.
"I missed pre-season then I had a run of games and I was really enjoying it.
"It is just disappointing to suffer something so niggly. But I think these injuries come from last season when I broke my leg."
Hargreaves' absence will be a blow to Ferguson, who already has a long injury list. Mikael Silvestre was ruled out for the season after suffering cruciate ligament damage at Goodison Park. Park Ji Sung and Ben Foster are currently recovering from similar injuries.
Wayne Rooney is hopeful of being involved in Lisbon after fracturing his foot on the opening day of the season and Ferguson said: "We took medical advice on Wayne and as he had only started training on (last) Monday, we felt that five days' training was maybe a bit short.
"But he trained on Saturday morning, Sunday and he'll train right through until Wednesday. By that point he will definitely be available for the match against Sporting."
Midfield duo John O'Shea and Darren Fletcher are definitely out after suffering knee injuries on international duty with the Republic of Ireland and Scotland last week
However, Sir Alex Ferguson was optimistic Hargreaves would be fit for the trip to Portugal, when United begin their quest to do better then last season's semi-final appearance.
But Hargreaves was unable to train on Monday morning and now appears resigned to setting his sights on the weekend game with Chelsea instead.
"It's okay, I have never really had this injury before so this is new territory," said the midfielder.
"I thought I would be fit for the Israel game, then the Russia game and then Everton, but I've still not done it. I have to take it day by day so hopefully I will be fit for the weekend.
"I can't say for certain but it looks as though I won't be ready for Wednesday because I have not trained."
Hargreaves believes this latest injury, allied to the tendinitis problem which effectively scuppered his pre-season programme and ruled him out of the Red Devils' opening two games against Reading and Portsmouth, is a legacy of the broken leg he suffered in Germany 12 months ago.
"It is frustrating," he said.
"I missed pre-season then I had a run of games and I was really enjoying it.
"It is just disappointing to suffer something so niggly. But I think these injuries come from last season when I broke my leg."
Hargreaves' absence will be a blow to Ferguson, who already has a long injury list. Mikael Silvestre was ruled out for the season after suffering cruciate ligament damage at Goodison Park. Park Ji Sung and Ben Foster are currently recovering from similar injuries.
Wayne Rooney is hopeful of being involved in Lisbon after fracturing his foot on the opening day of the season and Ferguson said: "We took medical advice on Wayne and as he had only started training on (last) Monday, we felt that five days' training was maybe a bit short.
"But he trained on Saturday morning, Sunday and he'll train right through until Wednesday. By that point he will definitely be available for the match against Sporting."
Midfield duo John O'Shea and Darren Fletcher are definitely out after suffering knee injuries on international duty with the Republic of Ireland and Scotland last week
