The glitzy party, held late on Thursday and hosted by actress Sharon Stone, is held every year during the Cannes film festival to raise funds for amfAR.
Clinton joined Stone, rapper 50 Cent, actor Robert Pattinson, singer Annie Lennox and members of the cast of Quentin Tarantino's film "Inglourious Basterds" at the exclusive Hotel du Cap-Eden-Roc to make the keynote speech to 800 guests.
"When times are tough you should give more, not less," he told diners in a giant marquee. "If it hurts a little more, we will still be happier," he added.
Clinton said around $30 trillion of wealth had been wiped out by the financial crisis between September and February. "But if you think about it, everyone in this room is better off than 99.9 percent of people who ever lived on planet Earth."
AmfAR chairman Kenneth Cole added: "When the economy slows down, the spread of AIDS speeds up."
One of the top lots at a fund-raising auction held on the night was a saxophone belonging to and signed by Clinton.
The instrument fetched 130,000 euros ($181,000), and the proceeds will be shared between The Foundation for AIDS Research (amfAR) and the Clinton Global Initiative.
Overall the auction raised $4.5 million for amfAR, which supports AIDS research, HIV prevention and treatment education, down from 2008's tally of more than $10 million.
Among the other highlights of the sale were two Bruce Weber prints which fetched 100,000 euros each, a trip to Milan Fashion Week (140,000 euros) and a customized case containing six bottles of vintage Dom Perignon rose champagne (50,000 euros).
Pattinson raised 40,000 euros by auctioning a kiss for the daughters of the two winning bidders.
Stone paid tribute to actress Natasha Richardson, who was an amfAR board member before she died after a skiing accident in March. Richardson's father Tony died of complications related to AIDS in 1991.