This study aims to evaluate the effects of smoking on extracellular heat shock protein levels. Heat shock proteins have been associated with numerous diseases. Studies on the relationship between smoking exposure and heat shock proteins were mostly evaluated with intracellular heat shock proteins. This cross-sectional case–control study was conducted on patients who applied to outpatient clinics for smoking cessation and routine control in our faculty hospital. Of the smoking men, 75 between the ages of 30 and 65 years and 82 nonsmoking men were included in the study. Heat shock protein levels in plasma samples were determined using ELX 800 plate reader and Human HSP ELISA kit. Plasma heat shock protein levels were found to be significantly higher in smokers. There is no significant relationship between all three heat shock proteins and age, the number of cigarettes smoked daily, and the number of cigarettes smoked so far (package/year) (p > .050). Smoking significantly increases plasma heat shock protein 90, heat shock protein 70, and heat shock protein 40 levels.