The objective was to evaluate the relationship between feed efficiency (FE), antioxidant activity (ANTI) and oxidative stress (OXI) in feedlot steers representing phenotypic extremes for FE. Steers (n = 182) were fed a 70 d growing phase (GP) diet of whole shell corn (GCorn) or roughage (GRough) in GrowSafe bunks at University of Missouri, then shipped to Iowa State University where the 12 greatest (HFE) and 12 least (LFE) efficient steers from each diet (n = 48; 467 ± 48 kg) were selected for evaluation. Steers received diets similar to GP diets and 3 d after arrival, blood was sampled to evaluate ANTI and OXI markers for GP. Steers were transitioned to finishing phase (FP) corn (FCorn) or byproduct-based diets (FByp) and on FP d 97, blood samples for FP were collected. Data for GP were analyzed as a 2 × 2, and data for FP as a 2x2x2 using PROC MIXED of SAS. Looking at GP diet effects, GRough had greater (P = 0.04) GP plasma protein carbonyl concentrations (PC) and a tendency for greater (P = 0.06) FP total blood lysate superoxide dismutase activity (SOD) than GCorn. The FByp had greater (P < 0.01) PC during FP than FCorn and no other FP diet effects were noted (P > 0.2). Analyzing FE group effects, during GP the HFE had greater (P < 0.04) PC and ratio of oxidized:reduced blood lysate glutathione concentrations than LFE. There were GP diet x FE group interactions, as LFE-GRough had greater (P ≤ 0.03) GP total SOD and greater (P ≤ 0.05) FP glutathione peroxidase activity (GPX) compared with LFE-GCorn and HFE-GRough; HFE-GCorn was intermediate. During GP, the LFE-GRough had greater (P < 0.01) GPX than other treatments and had greater (P = 0.03) plasma malondialdehyde concentrations than LFE-GCorn. No GP diet x FP diet, FP diet x FE group, or 3-way interactions were noted (P > 0.3). The GP diet and FE groups had stronger relationships with ANTI and OXI markers measured during the GP than the FP. Antioxidant activity may play a role in FE as LFE, driven largely by LFE-GRough, had greater SOD and GPX than HFE, potentially using a greater proportion of energy otherwise utilized for tissue accretion.