BACKGROUND: Imbalanced dietary patterns, sedentary behavior, and other unhealthy lifestyle behaviors are among the potentially modifiable risk factors most consistently linked to all-cause and cardiovascular disease (CVD) mortality. This study aimed to investigate the joint association of antioxidant intakes from diet and supplements and sedentary behavior with all-cause and CVD mortality. METHODS: This retrospective cohort study included 16,019 adults from National Health and Nutrition Examination Survey (NHANES) 2007-2014. All-cause and CVD mortality was ascertained by linkage to National Death Index records through 31 December 2019. Participants were divided into four lifestyle patterns based on their intake of six antioxidants from dietary intakes and supplements and their self-reported sedentary behavior: low-antioxidant diet and prolonged sedentary behavior, low-antioxidant diet and nonprolonged sedentary behavior, high-antioxidant diet and prolonged sedentary behavior, high-antioxidant diet and nonprolonged sedentary behavior. Multivariable Cox proportional hazards models were utilized to evaluate the associations of antioxidant diet and sedentary behavior with regards to all-cause and CVD mortality. RESULTS: Over an average follow-up of 8.5 years, a total of 1,894 overall deaths and 482 CVD deaths were reported. Compared with the low-antioxidant diet and prolonged sedentary behavior group, participants in the high-antioxidant diet and nonprolonged sedentary behavior group had a significantly lower risk of all-cause (hazard ratio [HR], 0.60
95% confidence interval [CI], 0.50-0.72) and CVD (0.51
0.34-0.77) mortality. Similarly, individuals following a low-antioxidant diet and engaging in nonprolonged sedentary behavior also had a reduced risk of all-cause (0.63
0.52-0.75) and CVD (0.54
0.38-0.76) mortality. On the other hand, there was no significant reduction in all-cause mortality among individuals in the high-antioxidant diet and prolonged sedentary behavior group (0.83
0.68-1.03), as well as CVD mortality (0.87
0.62-1.21). Subgroup and sensitivity analyses yielded results that were consistent with the overall analysis. CONCLUSIONS: Participants with both high-antioxidant diet and nonprolonged sedentary behavior had the lowest all-cause and CVD mortality. Additionally, nonprolonged sedentary behavior can help counteract the harms of low-antioxidant diet, whereas a high-antioxidant diet fails to offset the deleterious effect of prolonged sedentary behavior.