Objectives We aimed to assess associations between depressive symptoms, lifestyle, and somatic symptoms during the COVID-19 pandemic. Design A prospective, observational study using a self-designed questionnaire. Setting Three general practitioners’ (GP) offices in rural Germany. Participants 271 adult patients without manifest cardiovascular or pulmonary disease with (n = 82) and without (n = 189) hypertension reporting to our GP offices. Main outcome measures The reported increase of depressive symptoms (loneliness, sleeplessness, joylessness, listlessness) prior to the first documented case in Germany on 27.01.2020 (t0) as opposed to patients’ health perception during the Corona pandemic (t1) was the primary outcome measure. The secondary outcome measures were changes in physical activity (PA), dyspnea and angina in the two groups. Results Out of 271 patients (50.8 ± 16.8 years, 55.1% females), 1.5% were tested positive for COVID-19. Overall, listlessness (8.5%, p = 0.001), sleeplessness (5.2%, p = 0.001) and joylessness (4.2%, p = 0.003) were increased. Dyspnea significantly increased (9.2%, p < 0.001) and employment status worsened (6.5%, p < 0.001). There were significant associations between the increase of depressive symptoms, weight increase (p = 0.017), and reduction in physical activity (p = 0.046). However, after adjusting for age, hypertensive patients did not show more depressive symptoms (p = 0.704), dyspnea (p = 0.063) or angina (p = 0.432), nor was there any difference in PA (p = 0.906) compared to healthy individuals. Conclusions We demonstrate an association between the deterioration of depressive symptoms, weight gain, and reduced physical activity during COVID-19, both in hypertensives and healthy controls. Hypertension is no driver of symptom deterioration during the pandemic. The trial was registered in the German Clinical Trials Registry (DRKS00022157).