TUI said direct trips to the capital had been cancelled and that the country would no longer figure on lists of itinerant visits such as those by cruise ships.
The German operator stressed that the vast majority of its clients did not plan to visit Mexico City anyway but would rather go to the seaside resort of Playa del Carmen, "which has been spared by the crisis until now."
TUI nonetheless offered an alternative destination to those who had already booked their tickets, at no extra charge.
"Of the roughly 1,000 TUI clients now in Mexico, only four find themselves directly in the region" identified as an epicentre of the deadly virus, the company said.
Spokesmen for the leading German airline Lufthansa, and number two Air Berlin, said they had not seen a sudden drop in reservations for Mexican destinations.
"It is not a major issue for us yet," the Lufthansa spokesman told AFP.
Starting on Sunday however, the carrier has handed out leaflets on the disease to passengers on its daily flights to and from Mexico City.
Air Berlin noted that the German foreign ministry had not issued a warning on travel to Mexico for the time being.
Swine flu has already killed at least 103 people in Mexico and cases have also been identified in Canada and the United States.
The first recorded case in Europe was found in a man who recently returned to Spain from Mexico.