Reigning Tour de France champion Jonas Vingegaard suffered a broken collarbone and several broken ribs following a high-speed crash at the Itzulia Basque Country stage race.
Vingegaard, 27, was among several riders caught up in the incident which occurred on a bend on a descent.
Race leader Primoz Roglic and fellow Grand Tour winner Remco Evenepoel were also forced to abandon the race.
The remaining 35km of Thursday’s fourth stage were neutralised.
Only the six riders in the front group contested the stage win, with Louis Meintjes taking victory.
“It’s not the way you want to win,” the South African said.
Meintjes’ team Intermarche-Wanty said: “Our thoughts are with all the riders involved in the nasty crash. Safety and wellbeing of our colleagues, it’s all that matters.”
The crash occurred after one rider fell, leading to several others leaving the road. Ambulances attended the scene and Denmark’s two-time Tour de France winner Vingegaard was taken away on a stretcher.
Team Visma-Lease a Bike said Vingegaard is stable and conscious but remains in hospital “as a precaution”.
Belgian Evenepoel, the 2022 Vuelta a Espana winner, was taken to hospital, as was UAE Team Emirates rider Jay Vine whose team confirmed the Australian was “conscious and talking”.
Race organisers said the stage times would not be counted for the general classification.
Slovenian Roglic held a seven-second lead over Evenepoel after three stages, with Vingegaard a further seven seconds behind in fifth.
But Dane Mattias Skjelmose of Lidl-Trek now holds the overall lead by four seconds heading into the fifth of six stages.