Evidence suggests that sedentary behaviour is typically associated with poorer mental health. Unfortunately, the Covid-19 pandemic increased physical inactivity and stress worldwide, especially for groups whose daily activities were disrupted, such as office workers. Thus, the present studies aimed to reduce sedentary behaviour and stress in office workers, via a digital behaviour change intervention. In three studies, full-time office workers of different enterprises in Scandinavia were randomly assigned to a 3-to-4-month intervention engaging in active breaks, or a waiting list control group. Randomization was blocked for previous overall physical activity. Univariate repeated-measures mixed ANOVAs and multiple regression models were performed using self-report psychological measures (e.g., perceived stress), physiological and behavioural variables (e.g., resting heart rate, physical activity, measured via a wearable physical activity tracker), as main outcome variables. Overall, the intervention groups, compared to the control groups (time by group effects), were significantly more physically active, improved physiological markers, and reported less stress. We found a viable, agile, and scalable solution to combat sedentary behaviour stress for both in situ and remote office workers. Providing office workers with a pervasive digital solution to empower them to increase their physical activity level by performing active breaks during the workday might be effective in the light of the mental and physical health risks levels that office workers may experience.