Federer, who has just turned 32, comes to the tournament as defending champion but with his confidence dented by his shock second round exit at Wimbledon.
His world ranking is now at five, his lowest since 2003, and he is battling a back injury which refuses to ease and which caused him to withdraw from the Montreal Masters last week.
In his desperation to remain a contender, the Swiss has even started using a bigger racquet, a move that has yet to convince his hero, Pete Sampras.
"Roger's forehand is his bread and butter and if he's thinking twice about it, that's not a good thing," Sampras told US media.
But Federer needs something on which to focus to arrest his worrying slump.
The 17-time Grand Slam title winner was beaten in the first round at Gstaad last month by Germany's Daniel Brands, his third loss of the summer against an opponent ranked outside the top 50.
He was defeated at Wimbledon by Sergiy Stakhovsky and then lost in the Hamburg semi-finals to Argentine qualifier Federico Delbonis.
His defeat to Ukraine's world number 116 Stakhovsky brought to an end a run of 36 consecutive Grand Slam quarter-final appearances.
As a top-eight seed, five-time champion Federer starts in Cincinnati with a bye and will face the winner from two-time finalist Mardy Fish and German Philipp Kohlschreiber.
"I lost some time but I was very motivated to put my Wimbledon loss behind me. I didn't really want to pull from Montreal but it gave me more time to come here well-prepared," said Federer.
"Now I'm fit again mentally and motivated by this time of the year."
World number one Novak Djokovic takes the top seeding ahead of Wimbledon champion Andy Murray, who went out in the third round at Montreal, a victim of Latvian Ernests Gulbis.
Spain's David Ferrer will aim for his first summer hardcourt win after exiting early in Canada as the third seed while Rafael Nadal will be seeded fourth just in front of Federer.
With the US Open starting in two weeks' time, 2011 Cincinnati champion Sharapova is also battling a nagging injury.
In her case, it's a hip problem suffered in her second round loss at Wimbledon to Portuguese qualifier, Michelle Larcher De Brito.
It was an injury which forced Sharapova, without a title since Stuttgart in April, to sit out the Toronto tournament last week.
Four-time Grand Slam champion Sharapova has hired Jimmy Connors as her coach only weeks after splitting with Thomas Hogstedt and the pair have been training for several days in Connors' native Midwest.
Sharapova will begin play in the second round against either American Sloane Stephens or a qualifier.
"It feels great to be back in Cincinnati," Sharapova posted on Facebook. "Getting a good hit in muggy conditions."
Double Australian Open champion Victoria Azaranka has also had a rough ride since withdrawing before her Wimbledon second round match due to an ankle injury suffered in the first round.
The Belarusian, who now lives in the same Californian beachside neighbourhood as Sharapova, made a comeback in Carlsbad, where she was runner-up to Samantha Stosur and also accepted a wild card into Toronto.
But after losing that final in California she withdrew from Canada, complaining of a lower back injury.
Azarenka and Sharapova take the second and third seedings behind world number one Serena Williams.
Poland's Agnieskza Radwanska is seeded fourth ahead of China's Li Na, Italian Sara Errani, Petra Kvitova of the Czech Republic and eight seeded Wimbledon winner Marion Bartoli.
The Frenchwoman had to retire after one set in the Toronto third round with an abdominal injury coupled with exhaustion after suffering with a hamstring at Wimbledon and withdrawing from two summer hardcourt events in California last month.
"It's normal, I'm human. At the end of the day I can't be winning after winning after winning without feeling at some point a kind of exhaustion," said Bartoli.