Abstract Overweight and obesity are among the most prevalent and pressing health issues affecting Latino men, with rates of overweight and obesity among Latino men being 42% and 37%, respectively22. Within this group, Puerto Rican (PR) men are at especially high risk. In the Hispanic Community Health Study/ Study of Latinos, the highest rates of obesity were observed among PR men (40.9%)22, and PR men had a high prevalence of type 2 diabetes (16.2%) and hypercholesterolemia (48.2%)22. Thus, there is an urgent need to address obesity-related behaviors- such as diet and physical inactivity- in Puerto Rican men. Moreover, developing culturally tailored obesity interventions that target diet, physical activity and sedentary behavior in Puerto Ricans has the potential to address a critical public health need and provides a foundation for tailoring and disseminating future interventions to other cultures. This study has the active support of the Hispanic/Latino Health Community Advisory Board, the Puerto Rican Cultural Center, The Puerto Rican Agenda, additional Puerto Rican-centered and Latino organizations and individuals, the RUSH-BMO Institute for Health Equity, and the NIH-funded University of Chicago- Rush Institute for Translational Medicine. Although telehealth has been used to increase reach in weight loss interventions with hard-to-reach populations26, 27, few have focused on men or ethnic minorities8. Moreover, there are no published telehealth weight loss interventions focusing on healthy eating, physical activity, and sedentary behaviors, specifically targeting Puerto Rican men who are at high risk for obesity. We therefore propose a proof-of-concept study to determine if a telehealth intervention, tailored to target Puerto Rican men of varying levels of acculturation, is feasible and acceptable, and if it can achieve clinically meaningful weight loss. The “TeleSalud Healthy Eating, Physical Activity, and Sedentary Behavior Intervention” (TeleSalud HE-PA/SB) will consist of 4 months of twice-weekly classes on increasing healthy eating and physical activity and decreasing sedentary behavior, followed by a 4-month maintenance healthy eating, physical activity, and sedentary behavior intervention. This intervention will be compared to the “TeleSalud General Health” intervention, consisting of 4 months of twice weekly telehealth classes on general health issues, followed by a 4-month general health intervention. We will examine feasibility, acceptability, and intermediate process measures for diet (energy intake, percent calories from saturated fat, fruit & vegetable intake via the Block Food Frequency Questionnaire); physical activity/ sedentary behavior (metabolic equivalent of task (MET)-minutes/week and minutes of moderate to vigorous physical activity [MVPA] via the International Physical Activity Questionnaire and accelerometer-assisted minutes of MVPA); and social cognitive theory concepts (self-efficacy, outcome expectations, social su...