Tomas Vokoun made 27 saves and stopped three of the Sharks' four shootout attempts to remain unbeaten in his last six starts against San Jose. Alexander Radulov scored in the third period and again in the shootout as the Predators earned their league-best 43rd victory.
Evgeni Nabokov made 28 saves for San Jose and forced the shootout with a stunning glove save on Paul Kariya with a second left in overtime, but the Sharks still lost for the sixth time in eight games.
Guerin, acquired Tuesday from St. Louis in a deadline deal to add toughness and experience to a young team, wore No. 13 and looked active on a line with MVP Joe Thornton and Jonathan Cheechoo. But Nashville kept the big-name line off the scoreboard.
After Martin Erat and Radulov scored power-play goals in the third period to put Nashville ahead 3-2, rookie Sharks defenceman Marc-Edouard Vlasic tied it with a wrist shot through traffic with 4:08 left in regulation.
Steve Bernier and Matt Carle also scored for the Sharks, who played without injured captain Patrick Marleau and defenceman Scott Hannan in just their fourth overtime game of the season.
Vernon Fiddler also scored for Nashville.
San Jose acquired Guerin and defenceman Craig Rivet, who still hasn't played for San Jose since Sunday's trade with Montreal, to add a veteran presence to a team sorely lacking in experience. Nashville did the same two weeks ago by picking up Peter Forsberg from Philadelphia.
Bernier, who hadn't scored in his first four games since returning from the minors and an injury, beat Vokoun on the power play midway through the first period. Carle, who also served a stint in the AHL this season, added another power-play goal late in the first.
Nabokov stopped a penalty shot by Erat in the second period, but the Czech forward tied it with a snappy wrist shot during a power play with 13:31 to play. Forsberg picked up the second assist, his third point in six games with Nashville.
Radulov then tipped home Shea Weber's shot from the point with 5:07 to play, and the Predators were in position for their fourth win in five games - but Vlasic fired a shot over Vokoun's glove hand just 59 seconds later.
San Jose had a power play in the final three minutes of regulation, but couldn't score. Christian Ehrhoff took a hooking penalty with 39 seconds left in overtime, but Nabokov gloved Kariya's one-timer and rolled onto his back with one second left, forcing the shootout.
Notes: Sharks D Rob Davison thought he had scored his first goal of the season early in the second period, but the officials instead called a delay-of-game penalty on Vokoun for knocking the net off its moorings moments earlier. Sharks coach Ron Wilson wanted the goal to count because play continued while the net was askew. ... San Jose knocked Nashville out of the first round of the playoffs last year. ... Marleau has an upper-body injury, and Hannan has a lower-body injury.