In an effort to develop more effective therapy for neonatal K1 Escherichia coli infection, a murine hybridoma antibody to the O-side chain of E. coli lipopolysaccharides (LPS) and cefotaxime, alone and in combination, were evaluated for their therapeutic efficacy against experimental K1 E. coli infection due to a homologous O serotype in newborn rats. Infected rats received either the LPS antibody (3 mg kg −1), cefotaxime (100 mg kg −1 day −1) or a combination of the two. Overall, the survival rate of animals receiving cefotaxime (46%) was significantly greater than that of animals receiving the LPS antibody alone (20%). It is of interest that the combination of cefotaxime and the LPS antibody was significantly more beneficial than either agent alone, as shown by a greater survival rate (73%). These findings suggest that immunotherapy with antibodies directed to O-LPS may be a useful adjunct to antimicrobial chemotherapy in neonatal E. coli infection.