Natural antibodies (NAbs) are polyreactive, have low avidity, and are a product of B‐1 cells. Evidence suggests that NAbs may play a key role in immune defense in turtles, as increased total mucosal antibodies are associated with a decreased number of extracellular intestinal parasites. However, it is unknown if this trend extends to other types of pathogens and if avidity of the NAb to the pathogen is a factor in protection. We examined the relationship between a common intracellular bacteria in turtles—Salmonella—and NAbs. Plasma and mucosal samples were taken from red‐eared slider turtles. We measured levels and avidity of antibodies that bound to lipopolysaccharide (LPS), a component of Salmonella cell wall. We examined the relationship between these measures and the ability of plasma to kill Salmonella as well as infection status. Higher mucosal antibody levels were significantly associated with a decrease in likelihood of infection with Salmonella; however, plasma antibody levels were not. There was a trend for bactericidal ability of the plasma to be positively correlated with plasma antibody levels bound to LPS, but not mucosal antibody levels. Avidity was not significantly related to either killing capacity or likelihood of infection suggesting that only increased quantity and not better binding is responsible for the decreased likelihood of infection. These findings suggest that NAb regulation was sufficient to isolate the infection to the gastrointestinal tract of the turtles, allowing it to be cleared with the mucus layer. Our results add further evidence that turtles use a general, nonspecific NAb response to combat pathogens.