Seppi was eliminated by qualifier Dominik, Meffert 6-2, 5-7, 6-4 on the second day of the clay-court tournament. Seppi was beaten by Paul-Henri Mathieu in last year's Swiss Open title match.
No. 6-seeded Nicolas Kiefer, the only other seeded player on the court Tuesday, advanced to the second round with a 6-3, 6-2 romp over Gianluca Naso.
Also Tuesday Stephane Bohli beat Robin Roshardt, 6-2, 4-6, 6-4; Victor Hanescu topped Olivier Patience, 7-6 (7-4), 6-2; Jeremy Chardy defeated Luis Horna, 7-6 (7-5), 6-7 (6-8), 7-5; and Flavio Cipolla rallied for a 5-7, 6-4, 6-4 win over Jiri Vanek.
Top-seeded Stanislas Wawrinka, playing in his home country, takes on Bohli Wednesday in the second round.
Swim Week Miami Beach 2014 [PHOTOS]