Egan Bernal has pulled out of the Criterium du Dauphine to "rest a bad back," according to fellow Team Ineos rider Geraint Thomas.
Bernal, 23, was in seventh place in the overall standings, 31 seconds behind leader Primoz Roglic of Jumbo-Visma.
"I don't think it's a major issue but better to be cautious," said Thomas.
Saturday's stage was won by Lennard Kamna of Bora-Hansgrohe after he broke away with around 3km to go of 153.5km run from Ugine to Megeve.
The yellow jersey group came in around three minutes further back, with Roglic now only 14 seconds ahead of Groupama-FDJ's Thibaut Pinot going into Sunday's final stage.
Roglic suffered a crash earlier in the stage, but recovered to the main leaders' group.
Colombian Bernal has been in good form during the warm-up races for the Tour de France starting on 29 August, where he is defending champion.
It leaves 23-year-old Pavel Sivakov as Ineos' highest-placed rider at the Dauphine - he is 18th, three minutes 15 seconds down, having impressed in his domestique role during the race.
Thomas is 28th, more than seven minutes down, and Chris Froome is 60th, nearly 30 minutes down.
Bernal, four-time Tour winner Froome and 2018 champion Geraint Thomas, 34, are all competing at the Criterium - the final warm-up event, which will help Ineos decide who to select for cycling's biggest race.
Bernal won the Route d'Occitanie on 4 August, finishing nearly 10 minutes ahead of Froome, and was 26 minutes ahead of the Briton in last week's Tour de l'Ain.
Ineos' policy is that whoever is the strongest rider going into the final week of any Grand Tour will be backed by the whole team, and they would be unlikely to want to take three riders to the Tour who would normally be considered team leaders.
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Froome's form has fallen short of that of Bernal and Thomas as he recovers from terrible injuries sustained in a crash at last year's Dauphine, but he may be happy to play a 'super domestique' supporting role to Bernal and Thomas to rediscover his level.
And if Bernal's back problems persist, Froome, 35, may be considered an important back-up option for the team.
"[Bernal's] had two races before," Thomas told the race website. "He's got the racing he needs and it's just about making sure everything is 100% there and no issues."
Welshman Thomas said it had been difficult to find his own form.
"It's been a tough start," he said. "Obviously I was hoping to be a bit better. The numbers are good, I just need to chip off another kilo or so and I'll be perfect."
Fourth stage result:
1. Lennard Kamna (Ger/Bora-Hansgrohe) 4hrs 27mins 56secs
2. David de la Cruz (Esp/UAE-Team Emirates) +41secs
3. Julian Alaphilippe (Fra/Deceuninck-Quick Step) +56secs
4. Jack Haig (Aus/Michelton-Scott) +58secs
5. Kenny Ellisonde (Fra/Trek-Segafredo) +1min 2secs
49. Adam Yates (GB/Michelton-Scott) +14mins 29secs
58. Geraint Thomas (GB/Team Ineos) +16mins 2secs
109. Chris Froome (GB/Team Ineos) +26mins 54secs
General classification after stage four:
1. Primoz Roglic (Slo/Team Jumbo-Visma) 17hrs 45mins 32secs
2. Thibaut Pinot (Fra/Groupama-FDJ) +14secs
3. Guillaume Martin (Fra/Cofidis) +24secs
4. Mikel Landa (Esp/Bahrain-McLaren) +26secs
5. Daniel Felipe Martinez (Col/EF Pro Cycling) +26secs
25. Adam Yates (GB/Michelton-Scott) +26mins 14secs
31. Geraint Thomas (GB/Team Ineos) +20mins 37secs
65. Chris Froome (GB/Team Ineos) +53mins 23secs