Chris Froome (Sky) commands the strongest army, and he faces a small group of talented rivals, each of whom brings a set of weapons to the fight.
The route took riders over four category-two climbs and a category-three, before a push up the final category-three ascent.
Team Sky's Froome has a 10-second advantage on United States rider Tejay Van Garderen and Orica-Scott's Esteban Chaves looked impressive to move into third place overall at 11 seconds.
Froome increased his race lead over Tejay van Garderen to 10 seconds.
Behind, as Contador and Froome kicked on, only Michael Woods (Cannondale-Drapac) and Chaves could follow them while Vincenzo Nibali (Bahrain-Merida) lost 26 seconds and Romain Bardet (AG2R-La Mondiale) 49.
Stage 5 profiled as a typical Vuelta stage, with plenty of short, steep climbs and an intense finale that was destined to lead to time gaps. "Tejay and Roche are both still in the mix, and they have a few cards to play", Froome continued. "We arrived in the top four for the GC guys on the first hard climb and this is a good signal for the future".
The stage had breakaway written all over it, and the early break of nine riders contained a number of high-profile names, including Julian Alaphilippe (Quick-Step Floors) and Marc Soler (Movistar).
Orica-Scott rider Jack Haig was 25th on stage five and remains the best-placed Australian at 18th overall.
"Chaves showed he's one of the strongest climbs so far in the race", Froome added. The TT is not really in his favour.
But after a lot of them struggled through a hilly stage and then toiled on the race's first summit finish, Froome looks to be in command of a race that he has finished as runner-up on three occasions.
After a commendable day out ahead, the two leaders were reeled in with 8km remaining - but not before Rubio put in a little dig to distance Rossetto (although the Frenchman managed to turn the tables before the pack closed in).
While Contador was able to battle through his stomach bug, the same can not be said for Trek team-mate John Degenkolb who was forced to abandon ahead of stage five. Contador's bid for the overall took a major blow during the third stage, when he ceded three minutes to Froome. If Contador can retain that form for the remainder of the race, he could ride his way onto the podium.
"The climb was similar to all of the climbs previous year, a really fast run in and really steep", he said.