Objective: To determine effects of vaccination with siderophore receptor and porin (SRP) proteins derived from Salmonella enterica serotype Newport on milk production, somatic cell count, and shedding of Salmonella organisms in female dairy cattle. Animals: 180 female Holsteins. Procedures: Cattle were randomly assigned to receive Salmonella Newport SRP vaccine or control solution. Vaccine or control solution was injected 45 to 60 days before parturition, and cattle received a second dose 14 to 21 days before parturition. Milk production was monitored for the first 90 days of lactation. Feces for isolation of Salmonella and blood samples for detection of antibodies against Salmonella Newport were collected at day of first injection and at days 7 to 14 and 28 to 35 of lactation. Results: Cattle inoculated with Salmonella Newport vaccine produced significantly more milk (1.14 kg/d), compared with cattle injected with the control solution. Cattle administered the vaccine had significantly higher concentrations of circulating antibody against Salmonella Newport SRP proteins at 7 to 14 days and 28 to 35 days of lactation. Salmonella Newport was not recovered; however, Salmonella enterica serotype Agona was recovered from 31 (20.3%) cattle, but likelihood of recovery did not differ significantly between vaccinates and control cattle. Conclusions and Clinical Relevance: Administration of a vaccine against Salmonella Newport SRP proteins to healthy dairy cattle prior to parturition increased milk production, even in cattle without detectable shedding of Salmonella Newport or clinical signs of salmonellosis: Additional research is needed to clarify the mechanisms by which productivity was improved.