The San Lorenzo Department (in Spanish, Departamento San Lorenzo) is an administrative subdivision (departamento) of Santa Fe Province, Argentina.

It limits with the populous Rosario Department and the Paraná River in the east; and from there (going clockwise) with the departments of Constitución (south), Caseros (east), Iriondo (east and north) and San Jerónimo (north).

Other cities and towns are Aldao, Capitán Bermúdez, Carcarañá, Coronel Arnold, Fray Luis Beltrán, Fuentes, Luis Palacios, Puerto General San Martín, Pujato, Ricardone, Roldán, San Jerónimo Sud, Timbúes, and Villa Mugueta.

The San Lorenzo Department includes important ports on the Paraná River, such as the city of San Lorenzo itself and Puerto General San Martín (which ships 50% of the Argentine exports of soybean).

This area also forms part of the so-called Industrial Corridor that stretches south towards Rosario and reaches up to San Nicolás de los Arroyos.