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Since August 2020; the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b) in collaboration with UNICEF has been operating a COVID-19 field hospital at the Teknaf sub-district of Cox’s Bazar in Bangladesh. This paper is focused on estimating the effects of a history of tobacco smoking and pre-existing co-morbidities on the severity of COVID-19 infection among adult patients admitted into the aforesaid hospital. We conducted a retrospective data analysis of COVID-19 adult patients hospitalized from August 27, 2020 to April 20, 2022. Based on inclusion criteria; a total of 788 admitted patients were included in the analysis. We conducted a Chi-squared test and Fisher’s exact test for the categorical variables to see their associations. Multinomial logistic regression models were performed to explore the risk factors for the severity of COVID-19 infection. Among 788 patients, 18.4%, 18.8%, 13%, 7.1%, 3.4%, and 1.9% have had a history of smoking, hypertension, diabetes, chronic obstructive pulmonary disease (COPD), cardiovascular diseases (CVD), and asthma respectively. Overall, the mean age of the patients was 40.3 ± 16.4 years and 51% were female. In multivariate analysis, history of smoking and co-morbidities were identified as the risk factors for the severity of COVID-19 infection; the history of smoking was found linked with an increase in the risk of developing critical, severe, and moderate level of COVID-19 infection- notably 3.17 times (RRR = 3.17; 95% CI: 1.3–7.68), 2.98 times (RRR = 2.98; 95% CI: 1.87–4.76) and 1.96 times (RRR = 1.96; 95% CI: 1.25–3.08) respectively more than the patients who never smoked. It was evident that patients with at least one of the selected co-morbidities such as hypertension, diabetes, COPD, CVD, and asthma exhibited a significantly higher likelihood of experiencing severe illness of COVID-19 compared to patients without any co-morbidity. History of tobacco smoking and pre-existing co-morbidities were significantly associated with an increased severity of COVID-19 infection.