The US face a tough task in the 4x100 metres freestyle relay against an Australian team boasting the fastest two men in the world.
But there should be a medal of some colour for Phelps who is bidding to add three to his tally to overtake Soviet gymnast Larisa Latynina's record haul of 18.
Phelps must bounce back from a disappointing fourth place in the 400 individual medley in a race won by compatriot Ryan Lochte who now appears to have displaced his long-time rival as the best all-round swimmer in the world.
"When I touched the wall I guess I was in shock. I guess I still am," Lochte said after winning one of the most eagerly awaited duels of the Games.
"I trained my butt off for four years, I just feel it inside my gut that this is my year."
It was the first time Phelps had missed out on a medal at the Olympics since he was a 15-year-old at Sydney in 2000.
Having won a record eight golds in Beijing four years ago, he could on Saturday have become the first male swimmer to win the same event at three successive Games. That honour could now go to Japan's Kosuke Kitajima in the 100 breaststroke.
Kitajima won the 100 and 200 breaststroke double at Athens in 2004 and Beijing four years later. He qualified for Sunday's final sixth fastest overall, with South Africa's Cameron Van Der Burgh setting the fastest time.
BRITAIN MEDAL-LESS
Like Phelps, host nation Britain are still seeking their first medal after world champion Mark Cavendish was outmanoeuvred and upstaged in the cycling road race by Kazakhstan's Alexandre Vinokourov.
Their best hope is in the pool where Rebecca Adlington defends her 400 freestyle title against Italian glamour girl Federica Pellegrini and world number one Camille Muffat of France.
But Britain also have chances to make amends in the women's cycling road race where holder Nicole Cooke faces Italian world champion Giorgia Bronzini and Dutchwoman Marianne Vos who is hoping finally to land gold after five consecutive world championship silvers.
Saturday's first full day of competition belonged to China who topped the medals table with four golds including two imperious performances in the pool.
Sun Yang powered to their first male swimming gold in the 400 freestyle and 16-year-old compatriot Ye Shiwen won the women's 400 individual medley, smashing the world record by more than a second in the process.
Ye unleashed an incredible sprint over the concluding freestyle leg to surge clear of the favourite, Elizabeth Beisel of the United States.
In doing so she became the first woman to break a long-course world record since polyurethane bodysuits, which boosted buoyancy and triggered a slew of quickfire times, were banned in 2009.
China's Yi Siling had already become the first gold medallist of the Games in the 10-metre air rifle while compatriot Wang Mingjuan extended a 10-year unbeaten international record to win the women's 48-kg weightlifting crown.
Italy were second in the medals table with golds in archery and fencing.
Their men's archery team beat the top-ranked United States by a single point on the last arrow of the final and the fencers swept all three medals in the women's individual foil.
China look certain to land another gold on Sunday in the women's synchronised three-metre springboard diving final.
The Chinese dominate world diving and few would bet against victory for He Zi and Wu Minxia.
Day Two also sees the latest incarnation of the US basketball 'Dream Team', this time featuring LeBron James, Kobe Bryant and Kevin Durant, beginning their title defence against France.
Tennis world number two Novak Djokovic of Serbia begins his quest for singles gold against Italy's Fabio Fognini.
Britain's Andy Murray returns to the court where he lost the Wimbledon final to Roger Federer this month for a first-round match against Switzerland's Stanislas Wawrinka.
Federer survived a scare in his opening Olympic singles match against Colombia's Alejandro Falla on Saturday before prevailing 6-3 5-7 6-3.
Serena Williams also breezed past Serbia's Jelena Jankovic in straight sets, with U.S. First Lady Michelle Obama cheering her on.
