The region's chief administrator, Bhola Siwakoti, was among 44 wounded when a bomb exploded near the political rally at a stadium, said police chief Yogeswor Romkhani.
Earlier, Siwakoti had said several ethnic rights group were suspected in the first explosions. He said the groups had called a general strike in the area to try to disrupt the rally.
The groups are demanding greater autonomy in southern Nepal, saying the region has been neglected in favor of the more populated north. They have staged strikes, transportation shutdowns and demonstrations to press their demands for more seats in the national legislature and a guaranteed number of representatives in the administration. Some of the protests have turned violent, leaving at least 80 people dead.
Several senior leaders of Nepal's seven-party ruling alliance had attended the political rally in Birgunj, but none were injured.
Siwakoti had told The Associated Press that security had been stepped up, with hundreds of police guarding the city. "We have policemen guarding every corner of the city and all the entry points," he said.
Nepal is preparing for an April 10 election to create an assembly that will rewrite the constitution, a key part of the peace process that began when Maoist rebels gave up a decade-long armed revolt.