Background: Psoriasis is a chronic skin disease in which lifelong treatment is required. Recently, we faced COVID-19 pandemic where adherence to a prescribed drug could have been affected. Objectives: We conduct a study to assess this statement. Methods: The study was performed in Dermatology Department with Pharmacy database in the Hospital Universitario de La Princesa. A retrospective observational database study was performed, including all psoriatic patients with a biological therapy prescription between March 13 and May 31, 2020, with a paired control group between March 13 and May 31, 2019. Medication possession ratio (MPR) was used to determine the adherence. Results: A total of 244 patients were included in the cohort and 228 in the control group. We observed a decrease in the percentage of adherent patients of 40.0% in COVID-19 period. Overall, MPR was lower in the 2020 period than in 2019. MPRs by treatment and drug family, with the exception of etanercept, certolizumab pegol, and guselkumab, were significantly lower between the 2019 and the 2020 period. Conclusions: Adherence to a prescribed drug can be affected by different factors such as age, sex, income quintile, or stress. We have demonstrated a deep impact on adherence because of the situation created by COVID-19 pandemic. These data are in contrast with previously reported results where adherence was slightly affected, probably due to the different epidemiological situation in different countries. Further efforts are needed to be done to mitigate COVID-19 pandemic influence on the therapeutic adherence.