The tick-transmitted bacterium Borrelia afzelii consists of a number of antigenically different strains - often defined by outer surface protein C (OspC) genotype - that coexist at stable frequencies in host populations. To investigate how host antibody responses affect strain coexistence, we measured antibody cross-reactivity to three different OspC types (OspC 2, 3 and 9) in three different strains of laboratory mice (BALB/c, C3H and C57BL/6). The extent of cross-reactivity differed between mouse strains, being higher in C3H than BALB/c and C57BL/6. In one of three pairwise comparisons of OspC types (OspC2 vs OspC9), there was evidence for asymmetry of cross-reactivity, with antibodies to OspC2 cross-reacting more strongly with OspC9 than vice versa. These results indicate that the extent of antibody-mediated competition between OspC types may depend on the composition of the host population, and that such competition may be asymmetric. We discuss the implications of these results for understanding the coexistence of OspC types.