The Singapore Grand Prix that was scheduled for October 3 has been cancelled due to logistic concerns brought about by the Covid-19 pandemic.
F1 and the Singapore authorities agreed it will not be possible to hold the event in the context of immigration restrictions in the city state.
Turkey, China and a second race at Austin in the USA are all under consideration as replacements.
"To cancel the event for the second year in a row is an incredibly difficult decision but a necessary one in light of the prevailing restrictions for live events in Singapore," Colin Syn, deputy chairman of the race promoter, said on Friday in a statement.
"We would not be able to deliver a full event experience fans have come to expect over the years while safeguarding the health and safety of our fans, contractors, volunteers and staff," Syn added.
"Ultimately we have to be responsible, cautious and prudent."
Races in Turkey and China, postponed earlier this season, could replace Singapore, while the United States could also host a second race.
This is not the only uncertainty on the calendar for the second half of the 2021 season. At present, travelling to Brazil (7 November), Turkey or Abu Dhabi (12 December) would mean a quarantine on the return journey for the majority of F1 staff.
Australia (21 November) is also being cautious about opening its borders.
The sixth round of the season, on a calendar of 23, is underway this weekend on the streets of Baku, Azerbaijan.