Defender Ashley Cole, who would have won his 99th England cap on Friday, and striker Andy Carroll were the latest players to withdraw from the squad after being injured at the weekend, and while Cole should return for next Tuesday's game against Ukraine at Wembley, Carroll is likely to be out for six weeks.
Other absentees include striker Wayne Rooney and midfielder Scott Parker, but England will go into the Group H match in good spirits following their 2-1 friendly win over Italy in Berne last month.
Apart from losing on a penalty shootout to Italy in the quarter-finals of Euro 2012 in June, England manager Roy Hodgson is unbeaten in seven matches over 90 minutes since taking over on May 1.
And with England improbably ranked third in FIFA's world rankings, compared to Moldova's 141st, anything other than an England win will be a major surprise.
In an online debate with fans on Tuesday night, the coach was asked whether he had had the chance to pick his ideal starting line-up yet because of so many injuries.
Hodgson, 65, said: "Maybe not, we've been hampered by injuries to very important players. We lost Gareth Barry and Frank Lampard, for example, before the Euros, and Wayne Rooney wasn't available for the first couple of games.
"In the Italian game I decided to leave out one or two of the obvious senior players who I thought would have been important during the qualifiers.
"I don't think that I've been able to pick an ideal team as there have always been some important players missing."
Even with their injuries, England should repeat their wins over Moldova in the qualifiers for the 1998 World Cup, when England won 3-0 in Moldova in September 1996 and 4-0 at Wembley a year later.
Moldova have never qualified for the World Cup and have won only two of the 38 qualifiers they have played. They have not won any of their past 13 over the past seven years.
Their record in the recent qualifying competition for the European Championship was not much better: they won three and lost seven of their 10 games, but two of those wins were against San Marino and the other a 2-0 victory over Finland.
Moldovan coach Ion Caras told the website moldova.sports.md on Wednesday: "We do have confidence in our strength and our chance - however, this is slimmer than England's."
San Marino, Poland, Ukraine and Montenegro complete the make-up of Group H.
Although Rooney and Carroll are out of the side, England have plenty of attacking options.
Jermain Defoe, who should make his 50th appearance for England, should lead the line, with either Daniel Sturridge, Danny Welbeck or Theo Walcott in support.
Defoe came on as a substitute and scored the winner in England's 2-1 victory over Italy in Berne, his 16th goal for his country.
