The retailer, which includes the GAME and Gamestation stores, will not offer any EA games in March beyond snowboarding title SSX, according to Eurogamer.
Staff at the chain alerted the games website to the situation after a company-wide memo was sent this morning, revealing that FIFA Street 3, Tiger Woods 13 and Sims 3 Showtime will also not be stocked at GAME Group stores.
GAME said that anyone who pre-ordered Mass Effect 3 should place a fresh order for the game at another retailer, such as Amazon, Play, Zavvi and ShopTo. Those who placed a deposit for the pre-order at a GAME store should contact their local retailer.
in a statement issued following publication of Eurogamer's original report, GAME said that a "supply issue" was behind the decision not to stock Mass Effect 3.
"We currently have a supply issue with regards to Mass Effect 3, which means that GAME and gamestation will not be able to fulfil orders for Mass Effect 3 at this time," said the firm.
"We want to give customers as much notice about this as possible and provide them with a range of options ahead of launch.
"We appreciate that this is disappointing for our customers, and we apologise sincerely for the inconvenience that this will cause."
Anyone who pre-ordered Mass Effect 3 at a GAME store will be offered a "gesture of goodwill" - £5 worth of Rewards points to their card if they visit before March 16.
Customers who placed a deposit for the pre-order will be refunded in store credit, and also offered the £5 in points. Anyone who pre-ordered online will get an online voucher to the value of £5 that can used on any GAME websites.
HMV has confirmed that it will be stocking Mass Effect 3 as planned.
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It is the latest in a series of problems for GAME. Earlier today, it announced 35 store closures and that it is going to shut sister website gameplay.co.uk.
GAME recently received lender support to alleviate financial troubles following apparent concern by publisher EA.
The high street retailer's shares plummeted by 90% in 2011, despite £1 billion in annual turnover.
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Watch the Mass Effect 3 trailer below: