Williams who, having won the Australian Open last season, then took the rest of the year off to give birth to her baby daughter, was no match for her sister in round 3.
The 6-3, 6-4 defeat for Williams having only played a Davis Cup doubles match and exhibition matches was the 12 defeat to her sister in 29 match-ups.
Serena told the media afterwards “I haven’t played in over a year. It’s definitely not less disappointing. I wish it were, but it’s not. But then again, I wish it wasn’t. Then I wouldn’t be who I am.”
In a tournament full of surprises, Britain’s Jo Konta and Kyle Edmund, both departed from the tournament early, whilst Novak Djokovic on his comeback since surgery, suffered an early round loss.
Roger Federer, who went back to no.1 in the world rankings, following his success in Rotterdam last month, will hold onto top spot after Indian Wells even if he loses, as his rival Rafael Nadal, pulled out of the Californian tournament and the Miami Open next week through injury.