South Africa fly-half Handre Pollard was left out of their 33-man squad for the Rugby World Cup due to a calf injury, it was announced on Tuesday.
Centre Lukhanyo Am (knee injury) and lock Lood de Jager (chest illness) were other notable absentees for the September 8-October 28 global showpiece event.
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However, after the squad was announced at a Johannesburg TV studio, a press release said Pollard, Am and De Jager would be on stand by in case of injury or illness.
Better news for World Cup holders the Springboks is the inclusion of captain and flanker Siya Kolisi, who is expected to play again this month after recovering from a serious knee injury.
"We are going to have to vary things compared to the way we played last time (2019 World Cup)," said Kolisi, who in 2018 became the first black Test captain of South Africa.
"A lot of teams have got better, I also believe we have got better as a team and our hard work will show that."
Head coach Jacques Nienaber said: "This was one of the hardest selections we have ever had to make,"
"Any of the 42-man training squad would do a great job, but injuries have played a part in the final selection and time, unfortunately, ran out for some real champions.
"However, we said from the outset that we wanted to name the best 33 players for the World Cup, and after giving 38 players a run in the last four Tests we are pleased with the make-up of the group."
"We have picked a squad with a bunch of the players who can also cover alternative positions, which we will need in a very tough World Cup."
The absence of 65-time capped Pollard is a huge blow for the Springboks, who begin their title defence with a Pool B match against Scotland on September 10.
His injury in an English Premiership match in May leaves the Boks with only one specialist fly-half, Manie Libbok, in the squad.
While Libbok can be an extremely creative playmaker, he is an erratic goal-kicker, missing four of nine efforts in a warm-up victory over Argentina last weekend.
Pollard was flawless in the 2019 World Cup final triumph over England, succeeding with all eight kicks at goal for a personal tally of 22 points.
Like Pollard, outside centre Am would have been a certain starter against Scotland in Marseille, but has been sidelined by an injury sustained in Buenos Aires last Saturday.
Inside centre Andre Esterhuizen benefited from the loss of Am, as he might not have made the squad otherwise.
De Jager became ill last week in Argentina and his omission means places for both Marvin Orie and former Ireland lock Jean Kleyn, who were originally rivals for one spot.
Johannesburg-born Kleyn qualified for Ireland through residency and, after not playing for his adopted country for three years, was eligible to change allegiance.
However, the likely starting second-row partnership against the Scots in Marseille will be Eben Etzebeth and RG Snyman.
Head coach Jacques Nienaber was expected to name three scrum-halves, but chose four -- first choice Faf de Klerk plus Jaden Hendrikse, Cobus Reinach and Grant Williams.
South Africa will play two more warm-up matches, against Wales in Cardiff on August 19 and New Zealand in London six days later.
The World Cup title-holders then head to the Mediterranean island of Corsica for a training camp before completing preparations in the French city of Toulon.
After Scotland, the Springboks face Romania, Ireland, the number one ranked Test team, and Tonga in Pool B with the section winners and runners-up qualifying for the quarter-finals.
Props: Vincent Koch, Ox Nche (both Sharks), Steven Kitshoff (Ulster/IRL), Frans Malherbe (Stormers), Trevor Nyakane (Racing 92/FRA)
Hookers: Malcolm Marx (Kubota Spears/JPN), Bongi Mbonambi (Sharks)
Locks: Jean Kleyn, RG Snyman (both Munster/IRL), Eben Etzebeth (Sharks), Marvin Orie (Perpignan/FRA)
Back row: Siya Kolisi (Racing 92/FRA, capt), Kwagga Smith (Yamaha Jubilo/JPN), Marco van Staden (Bulls), Pieter-Steph du Toit (Toyota Verblitz/JPN), Duane Vermeulen (unattached), Jasper Wiese (Leicester Tigers/ENG)
Utility forwards: Deon Fourie (Stormers), Franco Mostert (Honda Heat/JPN)
Scrum-halves: Jaden Hendrikse, Grant Williams (both Sharks), Faf de Klerk (Canon Eagles/JPN), Cobus Reinach (Montpellier/FRA)
Fly-half: Manie Libbok (Stormers)
Wings: Kurt-Lee Arendse, Canan Moodie (both Bulls), Cheslin Kolbe (Suntory Sungoliath/JPN), Makazole Mapimpi (Sharks)
Centres: Damian de Allende (Saitama Wild Knights/JPN), Andre Esterhuizen (Harlequins/ENG), Jesse Kriel (Canon Eagles/JPN)
Full-back: Willie le Roux (Bulls)
Utility back: Damian Willemse (Stormers)