Firsthand and, to a lesser degree, secondhand tobacco smoking are considered the greatest causes of preventable illnesses and premature death worldwide. Firsthand and secondhand smoking have adverse consequences on the immune system, although these effects are not fully understood. A few serological studies have been done on firsthand and secondhand smokers in Saudi Arabia. The present study investigates the effects of firsthand and secondhand smoking on the immune system of randomly chosen male firsthand (50 subjects) and secondhand (50 subjects) cigarette smokers, residing in Jeddah, Saudi Arabia, with an age range of 20-40 years. Firsthand smokers were categorized according to the number of cigarettes smoked daily (frequency of smoking). Blood samples were collected and differential complete blood counts, cotinine concentrations, and antibodies (IgG, IgM, and IgA) concentrations were determined. Additionally, T, B, NK, CD4? and CD8? cells counts and percentages were determined. Compared to secondhand smokers, firsthand smokers showed a highly significantly higher mean cotinine concentration and a highly significantly lower mean IgA concentration. Additionally, Secondhand smokers had significantly higher mean lymphocyte count and CD4?/CD8? ratio, and significantly lower mean basophil and NK cells counts. All other parameters showed no significant differences between firsthand and secondhand smokers and there were no differences between the frequency of smoking categories for the firsthand smokers. Therefore, The results show suggest that passive and active smoking have different immunological effects since IgA levels and some white blood cells counts were different in firsthand and secondhand smokers. ImplicationsFirsthand and secondhand tobacco smoking are widely prevalent in Saudi Arabia and rates of smoking continue to increase. For the last few decades, diseases and conditions associated with smoking have been increasing in Saudi Arabia. There is a lack of studies on the effects of smoking on the immune system in Saudi Arabia and thus this study fills a gap and provides much-needed results on these effects. In addition, this study draws attention to the need for strong recommendations and the implementation of educational and cessation programs to reduce the negative impact of smoking in Saudi Arabia.