It was only the second time in 16 appearances in Monte Carlo that Spain's Rafael Nadal had failed to make it to the semi-finals.
The underwhelming performance of the reigning champions will most likely require them to beat Rafael Nadal's Spain to stand a chance of reaching the knock out phase.
Federer, a seven-time champion, was ousted from one of his favourite tournaments in barely over an hour, falling in straight sets to a 21-year-old Andrey Rublev he had never faced.
The 21-year-old German won his third title of the year and the ninth of his career by defeating Australian teen Alex De Minaur 6-2, 6-4 in the 50th edition of the US Open tuneup event.
Roger Federer's hopes of claiming a record-extending 20th grand slam title ended when he was beaten 7-5 3-6 7-6(8) 6-4 by Juan Martin del Potro in a thrilling US Open quarter-final.
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