Genetic selection for fast growth can affect the ability of male turkeys to cope with stressors, resulting in decreased immunity to opportunistic bacterial infection. The purpose of the current study was to compare the effects of ascorbic acid (AA) on the stress response and resistance to Escherichia coli challenge of birds selected for increased 16-wk body weight (BW; F-line) with their random-bred parent line (RBC2). Male turkeys were raised in duplicate floor pens in a two line × two AA treatment × two stress challenge (SC) design. At 5 wk of age, AA (1200 ppm) was provided in drinking water for a 24-hr period, during which all birds were weighed. After AA treatment, the SC group was subjected to a transport stress protocol. Six hours after the start of transport, SC birds were also inoculated in the thoracic air sac with 1 × 10⁴ colony-forming units of E. coli. The following morning four birds from each pen were bled, and all birds were weighed and necropsied 2 days later. BW and gain after SC were decreased in the F-line but not the RBC2 line, and there were no AA effects on BW. The weight of the bursa of Fabricius relative to BW was higher in the RBC2 line than in the F-line, was decreased by SC, and was not affected by AA. The heterophil∶lymphocyte ratio was higher in the SC F-line as compared to the SC RBC2 and was decreased by AA only in the SC F-line. Corticosterone (C) levels were increased by SC only in the F-line, and AA decreased C levels only in the RBC2 line. Airsacculitis scores were increased in the F-line SC birds. The challenge strain of E. coli was only detected in the air sac and liver of the AA-treated F-line SC birds and in the liver of the no-AA F-line birds. These results suggest that SC at 5 wk of age had a more deleterious effect on the fast-growing F-line than on its parent line and that AA may have increased susceptibility to colibacillosis in the SC F-line birds.