The peloton faced intermittent drizzle in Thursday’s 120-mile course from Arras to Reims, a mostly flat ride well suited for sprinters.
The race got its biggest surprise on Wednesday after defending champion Chris Froome, carrying from an injured wrist, dropped out of the race after crashing twice.
Two-time Tour champion Alberto Contador was dealt a setback after Saxo-Tinkoff teammate Jesus Hernandez dropped out after a crash.
Overall, Nibali has a two-second lead over teammate Jakob Fuglsang of Denmark. Slovakia’s Peter Sagan is third, 44 seconds back.
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