BACKGROUND: Coronavirus disease 2019 (COVID-19) lockdown restrictions may impact lifestyle and therefore also physical (in)activity patterns in patients with cardiovascular disease (CVD). This study aimed to evaluate the effect of lockdown on physical activity and sedentary behaviour. METHODS: A total of 1565 Dutch CVD patients participated in this prospective cohort study, in which we compared physical activity and sedentary behaviour before and during the COVID-19 lockdown period. Baseline measures were assessed in 2018 and data on follow-up measures were collected between 17 and 24 April 2020 (5 weeks after the introduction of COVID-19 lockdown restrictions). Validated questionnaires were used to assess physical activity and sedentary behaviour. RESULTS: Moderate-to-vigorous physical activities increased from 1.6 (0.9, 2.8) to 2.0 (1.0, 3.5) h/day [median (interquartile range)] (p < 0.001) during the COVID-19 lockdown, mainly due to an increase in time spent walking and doing odd jobs. In contrast, time spent exercising significantly declined [1.0 (0.0, 2.3) to 0.0 (0.0, 0.6) h/week], whereas sedentary time increased from 7.8 (6.1, 10.4) to 8.9 (6.8, 11.4) h/day (p < 0.001). The absolute increase in physical activity was 13 (-36, 81) min/day, whereas sedentary behaviour increased by 55 (-72, 186) min/day. CONCLUSION: Despite a small increase in physical activities, the larger increase in sedentary time induced a net reduction in habitual physical activity levels in Dutch CVD patients during the first-wave COVID-19 lockdown. Since a more inactive lifestyle is strongly associated with disease progression and mortality, we encourage CVD patients and their caregivers to explore novel solutions to increase physical activity levels and reduce sedentary time during (and beyond) the COVID-19 pandemic.