Background: Excessive sedentary time has been negatively associated with several health outcomes, and physical activity alone does not seem to fully counteract these consequences. This panorama emphasizes the essential of sedentary time interruption programs. "The Up Project" seeks to assess the effectiveness of two interventions, one incorporating active breaks led by a professional and the other utilizing a computer application (self-led), of both equivalent duration and intensity. These interventions will be compared with a control group to evaluate their impact on physical activity levels, sedentary time, stress perception, occupational pain, and cardiometabolic risk factors among office workers. Methods: This quasi-experimental study includes 60 desk-based workers from universities and educational institutes in Valparaiso, Chile, assigned to three groups: (a) booster breaks led by professionals, (b) computer prompts that are unled, and (c) a control group. The intervention protocol for both experimental groups will last 12 weeks (only weekdays). The following measurements will be performed at baseline and post-intervention: cardiometabolic risk based on body composition (fat mass, fat-free mass, and bone mass evaluated by DXA), waist circumference, blood pressure, resting heart rate, and handgrip strength. Physical activity and sedentary time will be self-reported and device-based assessed using accelerometry. Questionnaires will be used to determine the perception of stress and occupational pain. Discussion: Governments worldwide are addressing health issues associated with sedentary behavior, particularly concerning individuals highly exposed to it, such as desk-based workers. Despite implementing certain strategies, there remains a noticeable gap in comprehensive research comparing diverse protocols. For instance, studies that contrast the outcomes of interventions led by professionals with those prompted by computers are scarce. This ongoing project is expected to contribute to evidence-based interventions targeting reduced perceived stress levels and enhancing desk-based employees' mental and physical well-being. The implications of these findings could have the capacity to lay the groundwork for future public health initiatives and government-funded programs.