The 52-year-old Sefcovic is considered one of the favorites in the March 16 vote for the largely ceremonial post.
Sefcovic announced his candidacy on Friday after accepting an offer to run from the senior ruling leftist party of former Prime Minister Robert Fico.
Sefcovic joined the commission in 2009 and became a vice-president in 2010. He said he fully supports Slovakia's EU membership.
Bela Bugar, the leader of a junior ruling party of ethnic Hungarians, and Marian Kotleba, the chairman of Slovakia's neo-Nazi parliamentary party, are among those also running.
President Andrej Kiska announced earlier he won't be seeking a second term.