Aim: Quarantine due to the COVID-19 pandemic altered the supply and demand of health services. This, together with the ‘infodemic’ and generalized panic, could alter the patterns of self-medication in the population. The objective was to characterize the patterns of self-medication in four cities of Colombia during mandatory preventive isolation in 2020. Methods: This was a cross-sectional study done in four Colombian cities during mandatory national preventive isolation between June and September 2020. A sample of 397 adults who responded to an online survey, based on the Instrument for Systematic Data Collection for Self-medication ( Instrumento de Recolección Sistemática de Datos para la Automedicación–IRIS-AM), was obtained. The use of social networks (including WhatsApp) as the source of information about medications was explored. Results: The 397 people surveyed had a median age of 31.0 years, and 58.2% were women. The prevalence of self-medication during lockdown was 34.3% ( n = 136). Medications targeting the nervous system ( n = 117; 86.0% of those participants with self-medication) and the musculoskeletal system ( n = 68; 50.0%) were the most commonly used. Ten (7.4%) of the self-medicated patients reported doing so to prevent COVID-19, and 15 (11.0%) named social networks as the source of information. Conclusion: More than one-third of the participants reported self-medication during COVID-19 lockdown, mainly with analgesic-type nervous system medications. People who reported self-medication to prevent COVID-19 often got their information from social networks, the Internet, and WhatsApp. Plain Language Summary Self-medication during mandatory COVID-19 isolation Introduction: Self-medication refers to the use of medications to treat self-diagnosed disorders or symptoms, and it can lead to health problems. This habit is widely practiced by the people, especially in low- and middle-income countries. The objective was to characterize the patterns of self-medication in four cities of Colombia during mandatory preventive isolation in 2020 due the quarantine by COVID-19 explored pandemic. Methods: We made a cross-sectional study between June and September 2020, and a sample of 397 adults who responded to an online survey. The use of social networks (including WhatsApp) as the source of information about medications was explored. Results: The prevalence of self-medication during lockdown was 34.3% ( n = 136). Medications targeting the nervous system ( n = 117; 86.0% of those participants with self-medication) and the musculoskeletal system (strategies n = 68; 50.0%) were the most commonly used. Conclusion: People who reported self-medication to prevent COVID-19 often got their information from social networks, the Internet, and WhatsApp. These findings raise the possibility of designing pedagogical strategies on this topic.