Objective The COVID-19 pandemic has caused a global health crisis. This situation has affected the general population, especially the most vulnerable populations such as individuals with cardiovascular diseases. The main objective of this study was to analyse adherence to treatment and psychological well-being in hypertensive patients before and after the COVID-19 lockdown in Spain.Methods A cross-sectional study was performed in a Basic Health Area of Toledo, Spain. Adherence and psychological well-being (resilience, self-esteem, and health-related quality of life [HRQoL]) were measured in hypertensive patients, a group of patients before the COVID-19 lockdown and, in another group after the COVID-19 lockdown using a heteroadministered and anonymous questionnaire.A factorial multivariate analysis of variance (MANOVA) was applied for the outcome variables using pre- and post-COVID-19 lockdown assessment, gender, and age (< 65 years-old vs. ≥ 65 years-old) as independent variables. Univariate F follow-up tests were conducted within the multivariate significant overall differences.Results The sample of the present study included 331 hypertensive patients. The mean age was 67.68 years (SD = 10.94). Women comprise 53.5% of the sample and men account for the remaining 46.5%. A total of 144 questionnaires were collected before the COVID-19 pandemic and 187 questionnaires were collected after the onset of the pandemic and once the lockdown was over. MANOVA showed significant main effects for pandemic lockdown (F = 13.383, p < 0.001,) age group (F = 3.74, p = 0.003) and gender (F = 8.85, p < 0.001).Therapeutic adherence decreased after the lockdown (F = 15.393, p < 0.001). However, scores on resilience (F = 17.771, p < 0.001), self-esteem (F = 4.789, p = 0.029), and physical component of HRQoL (F = 13.448, p < 0.001) increased after the lockdown.Regarding age, the univariate test showed a significant effect for the physical component of HRQoL, with scores decreasing in those aged ≥ 65 years (F = 9.375, p = 0.002). Regarding gender, women scored lower on resilience (F = 20.280 p < 0.001), self-esteem (F = 18.716, p < 0.001), the physical component of HRQoL (F = 5.722, p = 0.017), and the mental component of HRQoL (F = 28.912, p < 0.001).ConclusionsThe COVID-19 pandemic had a negative effect on treatment adherence of hypertensive patients in Spain. However, variables related to psychological well-being have increased in these patients, which may serve as a protective factor against pandemic stress.