Overweight and physical inactivity are associated with elevated reactive oxygen species and chronic low-grade inflammation. Exercise training studies have measured changes in systemic inflammatory and oxidative/antioxidative biomarkers but predominantly at moderate-high intensities. Few low-intensity, lifestyle-based physical activity (PA) studies have been conducted. Purpose: To determine whether improvements in lifestyle-oriented PA resulting from a 16-week internet-delivered PA program (ALED-I) elicit cardioprotective improvements in measures of inflammation, oxidation, or antioxidant enzyme capacity. Methods: Forty-one men and women (23-62 years) were randomized to either the ALED-I intervention (n =19; age=40.4±1.9 yrs; BMI=31.4±1.1 kg/m²) or a delayed intent-to-treat control condition (n =22; age=46.6±1.3 yrs; BMI=31.0±0.7 kg/m²). Tumor Necrosis Factor- (TNF-), C-Reactive Protein (CRP), myeloperoxidase (MPO), superoxide dismutase (SOD), catalase (CAT), total antioxidative capacity (TAC), change in PA and other cardiometabolic disease risk factors were measured at baseline and post-intervention. Results: The ALED-I group increased PA and decreased central adiposity without changes in the control group. There was no change in the control group for any inflammation, oxidation, or antioxidant biomarkers. TNF- decreased (p=0.01) in the intervention group, but was not statistically different than control group. Conclusions: Modest improvements in daily low-intensity ambulatory PA as a result of an internet-delivered lifestyle PA intervention may be cardioprotective in sedentary and overweight adults through reductions in central adiposity and inflammation. However, the absence of favorable changes in other inflammation, oxidation and antioxidant biomarkers highlights the need for further attention to the dose-response of lifestyle-structured PA promotion strategies for health maintenance/improvement.