Concerns, behaviours, and beliefs influence how people deal with COVID-19. Understanding the factors influencing adherence behaviour is of utmost importance to develop tailored interventions to increase adherence within this context. Hence, we aimed to understand how COVID-19 affected adherence behaviour in Portugal. A cross-sectional online survey was conducted between 1 March and 3 April 2021. Descriptive statistics were performed, as well as univariable and multivariable regression models. Of the 1202 participants, 476 who were taking at least one medication prescribed by the doctor were selected. Of these, 78.2% were female, and the mean age was 40.3 ± 17.9 years old. About 74.2% were classified as being highly adherent. During the pandemic, 8.2% of participants reported that their adherence improved, while 5.9% had worsened adherence results. Compared with being single, widowers were 3 times more prone to be less adherent (OR:3.390 [1.106–10.390], p = 0.033). Comorbid patients were 1.8 times (OR:1.824 [1.155–2.881], p = 0.010) more prone to be less adherent. Participants who reported that COVID-19 negatively impacted their adherence were 5.6 times more prone to be less adherent, compared with those who reported no changes (OR:5.576 [2.420–12.847], p < 0.001). None of the other variables showed to be significantly associated with pharmacological adherence.