World number four Petra Kvitova bowed out of the Rogers Cup on Wednesday, as did former number ones Caroline Wozniacki and Jelena Jankovic.
Petra Kvitova fell to former world number one Victoria Azarenka at the Rogers Cup on Wednesday, in the biggest shock of the tournament in Toronto.
Third seed Kvitova played the WTA Premier hard-court event despite being diagnosed with mononucleosis in the days leading up to it, and she was unable to get a win - going down to Azarenka 6-2 6-3.
The two-time Wimbledon champion had withdrawn due to fatigue on multiple occasions earlier in the 2015 season, and the world number four's future remains unclear.
Kvitova was joined in an early exit by Wimbledon finalist Garbine Muguruza - the eighth seed going down to qualifier Lesia Tsurenko 7-5 6-1.
Fourth seed Caroline Wozniacki, French Open runner-up Lucie Safarova and 11th seed Ekaterina Makarova were other surprise losers.
Former number one Wozniacki fell to Belinda Bencic 7-5 7-5, the Swiss teen backing up her tough three-set win over Eugenie Bouchard.
Seventh seed Safarova served for a two-set win, but succumbed to Daria Gavrilova 4-6 7-5 7-5, while Makarova was denied by qualifier Polona Hercog 6-2 6-7 (2-7) 7-5.
World number 11 Angelique Kerber must like her chances of the title in Montreal, after a comfortable 6-2 6-3 win over qualifier Monica Puig.
Kerber is on a 16-2 win-loss run dating back to the French Open - both of those losses to the now-eliminated Muguruza.
Sixth seed Agnieszka Radwanska ended lucky loser Julia Goerges' run with a 7-5 6-3 result, while Sara Errani - seeded 15th - did it tougher to see off Madison Brengle 6-3 2-6 6-3.
German qualifier Carina Witthoft is into the last 16, after seeing off Alison Riske 6-4 5-7 6-3, while fellow qualifiers Olga Govortsova, Heather Watson and Mirjana Lucic-Baroni bowed out.
Fifth seed Ana Ivanovic battled past Govortsova 6-4 7-6 (7-4), Watson fell to 16th seed Andrea Petkovic 6-4 6-3 and Lucic-Baroni lost to the in-form Roberta Vinci 6-3 6-3.
Petkovic earned herself a date with top seed Serena Williams in the third round - the only other all-seed clash in the last 16 will see Kerber do battle with second seed Simona Halep, who was a 6-3 6-4 winner over Jelena Jankovic.
Alize Cornet was too good for Dominika Cibulkova 6-3 6-2, while Sabine Lisicki held off Barbora Strycova 7-6 (7-3) 6-4.