United Nations chief Antonio Guterres has slammed restrictions targeting southern African nations as a form of racist travel segregation.
European nations are among countries that have imposed travel curbs after the detection of the COVID variant Omicron.
"We have the instruments to have safe travel," said Guterres following talks with African Union Commission Chairman Moussa Faki Mahamat.
"Let's use those instruments to avoid this kind of ... of, allow me to say, travel apartheid -- which I think is unacceptable."
Apartheid was a brutal system of institutionalised racial segregation that existed in South Africa in which black people and people from other racial groups did not have the same political and economic rights as white people and were forced to live separately from whites.
The travel curbs target several countries after health experts tracking infections in the region first identified the Omicron variant.
"What is unacceptable is to have one part of the world, that is one of the most vulnerable parts of the world economy, condemned to a lockout when they were the ones that revealed the existence of a new variant that's, by the way, already existed in other parts of the world, including in Europe, as we know. So there is a very strong appeal that I launch, appeal to common sense," Guterres said.
The UN chief warned that the wave of travel restrictions risks jeopardising Africa's economic recovery and will not really stop the spread of the virus around the world.
Netherlands finds earlier cases of Omicron variant
Earlier this week, the Netherlands' public health institute reported two local cases of the Omicron COVID-19 variant dating back to November 19 and 23.
The cases predate those found in passengers that arrived in Amsterdam from South Africa on November 26.
Many other European countries -- including Spain, Portugal, Denmark, Germany, the Czech Republic, Italy, and Belgium -- have announced that they have detected cases of the new coronavirus strain.
On Monday afternoon a hospital in Madrid announced an Omicron case in a 51-year-old man who had returned to Spain from South Africa on Sunday and was showing mild symptoms.
Earlier Portugal said it had detected its first cases of the Omicron variant associated with players of the Belenenses SAD football club.
The country's public health agency said preliminary tests suggested that all 13 cases associated with players are related to the Omicron. One of the players had travelled to South Africa, where the variant was first detected.
Speaking at a press conference on Sunday, European Commission President Ursula von der Leyen said a "race against time" was underway to tackle the Omicron variant.
WHO on Omicron risk level
The World Health Organization said the Omicron variant had a high number of mutations, some of them concerning and pointing to "immune escape potential and higher transmissibility."
That means it is uncertain if the current COVID-19 vaccines will work against it and that the variant has the potential to spread faster.
Experts in South Africa said the variant was likely behind a "rapid rise in cases" in the last two weeks in the country but that it was too early to tell if the variant was more severe.
WHO urged countries to "ensure mitigation plans are in place to maintain essential health services" in case of a potential hospitalisation surge.
The first case of Omicron was detected in South Africa on November 9. South Africa's health minister Dr Joe Phaahla condemned recent travel bans as "counterproductive" given that many countries have now reported cases.