Britain’s Chris Froome has fallen to 14th place at the Ruta del Sol after a puncture on the fourth stage.
The four-time Tour de France winner trailed in one minute 19 seconds behind Saturday’s stage winner Tim Wellens, having started in seventh overall.
Lotto-Soudal’s Wellens and Movistar’s Mikel Landa broke away from the pack and it was the Belgian who prevailed by five seconds to claim the red jersey.
Froome’s Team Sky colleague Wout Poels, who led after three stages, was fourth.
The Briton is competing for the first time since an adverse drugs test was made public.
He has to explain to cycling’s world governing body, the UCI, how he returned double the allowed level of legal asthma drug Salbutamol in his urine during his Vuelta a Espana victory in September.
Stage four result
1. Tim Wellens (Bel/Lotto-Soudal) 4hrs 36mins 23secs
2. Mikel Landa (Spa/Movistar) +5secs
3. Jakob Fuglsang (Den/Astana) +12secs
4. Wout Poels (Ned/Sky) +13secs
5. Floris de Tier (Ned/LottoNL-Jumbo) same time
6. Marc Soler (Spa/Movistar) +17secs
7. Steven Kruijswijk (Ned/LottoNL-Jumbo) +20secs
8. Luis Leon Sanchez (Spa/Astana) same time
9. Simon Clarke (Aus/EF Education First-Drapac) +21secs
10. Andrea Pasqualon (Ita/Wanty Groupe Gobert) +24secs
1. Tim Wellens (Bel/Lotto-Soudal) 17hrs 24mins 25secs
2. Mikel Landa (Spa/Movistar) +7secs
3. Wout Poels (Ned/Sky) +11secs
4. Jakob Fuglsang (Den/Astana) +14secs
5. Luis Leon Sanchez (Spa/Astana) +20secs
6. Marc Soler (Spa/Movistar) +32secs
7. Steven Kruijswijk (Ned/LottoNL-Jumbo) +58secs
8. Simon Clarke (Aus/EF Education First-Drapac) +65secs
9. Mikel Bizkarra (Spa/Euskadi-Murias) +74secs
10. Sergio Pardilla (Spa/Caja Rural-Seguros) +84secs