The aim of this study is to evaluate medical expenditures and lost productivity associated with burden of Salmonella infections. We used laboratory confirmed number of Salmonella cases and corresponding multipliers to estimate the burden of illness using the method adopted by Foodborne Diseases Active Surveillance Network (FoodNet) at Centers for Disease Control and Prevention (CDC). The medical costs estimates are retrospective analysis of reimbursement records from MarketScan data. We identified patients with a diagnosis of salmonellosis using ICD-9 CM codes from the MarketScan 1993-2001 databases. Productivity loss from the nonfatal cases of Salmonella was calculated using the distributions of lost workdays and household services due to the illness. Statistical value of life approach was used to estimate the costs due to premature deaths. We also compared the costs for the gastrointestinal salmonellosis to the cost for the invasive salmonellosis. Confidence intervals around the cost estimates were calculated using a Monte Carlo simulation technique. Estimated average economic burden due to Salmonella was $210 per outpatient, $5,797 per inpatient with gastrointestinal infection, $16,441 per impatient with invasive infection and $4.63 million per premature death. Total economic buren due to Salmonella in the United States was estimated at $2.8 billion (95% CI: $1.6 to $5.3 billion) annually, which is approximately $2,472 per case of Salmonella infection. The cost estimate is largely driven by the number of premature deaths followed by average cost of hospitalization. Defining the risk factors for fatal outcomes may help target treatment and preventive strategies.