Argentine striker Franco Di Santo signed a three-year deal at German club Werder Bremen during the summer transfer window in 2013 after he was released by Wigan Athletic in the English league. His transfer to Bremen was announced officially on April 14, 2013. Nine days later, he made his debut for the clubin the league as a 67th minute substitute for Austrian star Marko Arnautovicduring the 1-0 defeat to Borussia Dortmund.

Franco Di Santo was sent off for a bad challenge on Bastian Oczipkaduring the 3-0 home league defeat to Eintracht Frankfurt on September 14, 2013.Oczipka needed facial stitches after the challenge from the striker. Two months later, he scored a goal and provided an assist for Dutch winger Eljero Elia in the final five minutes but it was not enough for Bremen who lost 3-2 at home to Mainz. Franco Di Santo finished his debut season at Werder Bremen with four goals in 23 league appearances.

Argentine striker Franco Di Santo was the main man for Bremen when they recorded their first league win of the season after ten games. Bremen recorded their first win of the 2014/15 season on November 1, 2014 at the expense of home team Mainz. Di Santo scored twice as Bremen came from behind to beat Mainz and end their nine-game winless run at the start of the season. With his brace against Mainz, Franco Di Santo took his tally to six goals in the league thus making him the joint leading goalscorer in the German Bundesliga at the start of November 2014. He scored his second brace of the 2014/15 league season to secure three points for his team against Hertha Berlin. Di Santo scored 13 goals in 26 league games by the end of his second and final season at Werder Bremen.