Salmonellosis ranks among the most frequently reported zoonosis worldwide and is often associated with foodborne outbreaks. Since the 1950s, the distribution of Salmonella serotypes in Sao Paulo State, Brazil, has been documented and periodically reported. In this study, we updated the data on the distribution of Salmonella serotypes received in our reference laboratory, isolated from human infections and nonhuman sources, from 2004 to 2020. In that period, a total of 9,014 Salmonella isolates were analyzed, of which 3,553 (39.4%) were recovered from human samples, mainly of stool (65%) and blood (25.6%), and 5,461 (60.6%) were isolated from nonhuman origins, such as animals (47.2%), food (27.7%) and animal environments (18.6%). In human isolates, a total of 104 serotypes were identified and the most frequent ones were Enteritidis, Typhimurium, S. I. 4,[5],12:i:-, Dublin and Typhi. A consistent reduction of the Enteritidis proportion was observed over the years. Among the 156 serotypes identified in isolates with nonhuman origins, Enteritidis, Mbandaka, Typhimurium, Agona and Anatum were ranked as the top five Salmonella serotypes; in more recent years, S. Heidelberg has increased in frequency. Although with different proportions, the top 10 prevalent serotypes were identified in both human and nonhuman origins, underscoring the role of animals, food products and environment as reservoirs of Salmonella with potential to cause human salmonellosis.