Background: The COVID-19 pandemic has heightened awareness of infectious illnesses and their links to host variables and underlying disorders. Objectives: In this review, we look at current research on a possible link between smoking and COVID-19 and study the biomarker changes in patients. Material and Methods: A case-control study included 45 smoker’s patients with COVID-19 and 50 healthy subjects as a control group who visited Al-Basra Teaching Hospital and Allmwanei Hospital in Al-Basra province between October 2021 and February 2022. The age average for the study population was (25-80) years. Serum and blood levels of human CBC, ESR, CRP, Ferritin, D-Dimer, IL 6, Albumin, FBS, HbA1c, Troponin, Cholesterol, Triglyceride, HDL, LDL, VLDL, Creatinine, Urea, Uric acid and GFR were measured. Results: The results show all biomarkers tend to have high sensitivity and specificity for smoker COVID patients based on the ROC curve analysis: Lymphocyte, CRP, Ferritin, D-Dimer, IL 6, Albumin, FBS, HDL, Creatinine, Urea, and GFR. These biomarkers might be helpful in determining the kind and severity of COVID-19 in smokers. Although the data is limited to a total number of patients. Conclusion: Studying patient alterations and vital signs led to the conclusion that smoking and COVID-19 are related. It was also verified that all vital indicators had strong sensitivity and specificity for smoking COVID patients.