The objective of this study was to determine the prophylactic efficacy of two commercial products, soluble vitamin E and soluble sodium salicylate (Uni-Sol^®), in an Escherichia coli respiratory challenge. The drinking water of male turkey poults was non-supplemented or supplemented with either vitamin E or Uni-Sol or a combination of both at dosages recommended by the manufacturer. There were 110 birds in each of the four treatments, housed in four floor pens per treatment. At 5 wk of age, birds in half of the pens were challenged with an air sac inoculation of approximately 50 colony-forming units of E. coli. Water treatment commenced 5 days before challenge and continued for 2 wk after challenge, when birds were necropsied. All water treatments prevented the decrease in body weight due to E. coli challenge; however, either vitamin E or Uni-Sol alone, but not the combination of the two, decreased body weight in nonchallenged controls. Either vitamin E or Uni-Sol treatment alone, but not the combination of the two, significantly decreased mortality and air sacculitis scores of challenged birds, and all treatments decreased the isolation rates of E. coli from the liver. All treatments protected liver, spleen, and bursa weights (relative to body weight) from the effects of E. coli challenge, and Uni-Sol alone or vitamin E with Uni-Sol protected relative heart weights from the effect of challenge. Uni-Sol treatment alone increased the main effect mean total leukocyte counts and the number and percent of lymphocytes. Uni-Sol in combination with vitamin E increased the number of lymphocytes of challenged birds. Uni-Sol alone decreased the main effect mean heterophil/lymphocyte ratio (H/L) ratio, whereas vitamin E alone increased the H/L ratio of challenged birds. These results indicate that treatment of turkey poults with vitamin E or Uni-Sol prior to and during the stressful events that can lead to colisepticema may decrease disease incidence and mortality.