Williams, 36, has played only a handful of matches this year but the three-times French Open champion has looked so unsafe in her black bodysuit in Paris that she seems capable of defying conventional wisdom and reclaiming the title.
A pectoral muscle injury had slammed the brakes on the ruthless Williams's serving arm so she decided not to take up the opportunity to extend her 14-year, 18-match win streak over the Russian.
She said: "Unfortunately I've been having some issues with my pec muscle". "At least all the stuff I read and the quotes that I read, which was a little bit disappointing", she said. "But I try to improve this thing, and I try to enjoy my nerves, because they are special when you play in a Grand Slam".
"Especially having a daughter, I feel like negativity is taught".
"And I have made every sacrifice that I could".
Williams' return to the French Open was a stunning comeback, after she gave birth to a daughter a year ago and suffered from blood clots and postpartum complications that made for a hard recovery.
"I'm beyond disappointed. I gave up so much from time with my daughter & time with my family all for this moment".
Despite her fine record against the Russian, Williams - who was playing in only her third tournament since giving birth - felt unable to put her body through the rigors of clay-court tennis ahead of the imminent grass-court season. "So it's really hard to be in this situation", the United States star added.
Serena Williams has pulled out of her French Open clash with Maria Sharapova due to injury. Sharapova by her own admission failed to read the email and was subsequently banned for two years, reduced to 15 months on appeal.
Since Tuesday last week, she had played six matches in six days, with her singles duties alternating with doubles alongside sister Venus.
Williams replied: "I honestly don't have any thoughts about that".
Sharapova spoke of her rivalry with Williams extensively in her autobiography a year ago.
If history is anything to go by, Williams is likely to win, but former men's champion Mats Wilander says this is Sharapova's best chance to get back on top.
Monday would have been the first time the pair played against each other in two years.
Sharapova gets a walkover as a result of Serena's withdrawal and will face either third seed Garbine Muguruza or Lesia Tsurenko in the last eight.
In his article, he wrote: "I asked Serena about comments President Donald Trump made to me in 2004 about her and Maria Sharapova".
In the same press conference, Williams addressed more questions about Sharapova and their rumored feud. "She didn't want to lose to me again".