Leagas will be included in any pitch for the estimated £10 million account.
The review kicks off next month.
Leagas was appointed to the pan-European account in September 2001. It launched Opodo's UK services in 2002 with a £3.5 million press and television campaign.
The TV ads used the Iggy Pop track Lust for Life, and the line: "Your flights on your terms ... and about time too."
The review follows a string of business losses for Leagas. In March this year, Harrods announced a review of its £2 million account, which is currently being handled by The Haystack Group. Leagas was also hit by the loss of the £12 million Hyundai account in February, which was its biggest-billing UK client.
The losses outweigh the agency's wins, which included Twinings in February and more recently a brief from the United Nations.
The review will not affect Opodo's media agency, MediaCom, which was appointed in September last year.
The creative review will be conducted by Neil Mott, Opodo's new UK country manager. He took up the position last October.
An Opodo spokeswoman said the contract had come up for renewal after three years with Leagas. She confirmed Opodo would talk to other agencies but added that the company was satisfied with Leagas' work to date.
Opodo launched in 2001 as a European joint venture between nine national air carriers including British Airways, Air France, Aer Lingus, Lufthansa, Iberia and KLM. The company offers flights, hotels, packages and insurance.
Currently operating in France, Germany and the UK, it plans further expansion into Europe this year.
Mark Gerrard, the board head of account management at Leagas, denied that a review was taking place.