There are few theories and little empirical evidence about the bilateral impact of substance use and coronavirus disease 2019 (COVID-19), so a logical and accurate picture of this area is required. We investigated the effects of opium use on severity of disease on hospitalized COVID‐19 patients in east of Iran. Demographic and clinical characteristics, vital signs, laboratory tests, mortality rate, type and duration of opium consumption in hospitalized patients who recovered from COVID-19 in the follow-up after 3 months were evaluated. In this study, 60 (20%) participants were the opium user and 251 (80%) were the non-user patients. Based on clinical symptoms, hypertension and systolic blood pressure in opium user were significantly higher than non-user patients (
p
< 0.05). In the laboratory tests, only the level of urea was higher in the opium positive group (37 [26.5–48.5] vs. 32 [23–43], respectively) and the percent of lymphocytes were lower in the opium positive (17 [8.2–25.8] vs. 18.7 [13.85–26.35], respectively). The initial therapies of both opium positive and negative infected patients showed not any significant changes (
p
> 0.05). Among the studied groups, one deceased case with COVID-19 was related to a drug user patient. Although, uses of opium reduced the levels of some risk factors, vital signs at admission and initial therapies during hospitalization in COVID-19 patients but it increased lung and heart diseases. Also, the severity of COVID-19 including hospitalization and mortality were associated with opium consumption.