Background: With increased cigarette smoking worldwide, greater numbers of inflammatory diseases have been recorded. Coronary diseases, pulmonary diseases, and cancers of different types are all associated with cigarette smoking. In Saudi Arabia, people start smoking at an early age, which could lead to acceleration in immune system issues. The presence of biological parameters that could be used to diagnose possible inflammatory mechanisms would speed the discovery of new therapeutic approaches. Methodology: In this study, we examined the concentration of AAT, TNF-α and MMP9 in serums for smokers and nonsmokers in the young Saudi male population, aged 19 to 35 years old. Results: The recorded data showed a significant increase in both TNF-α and MMP-9, with mean ± SEM as 239.5 ± 43.14 vs. 83.02 ± 11.96 with P values of 0.0004 (3571 ± 542.5 vs. 1718 ± 137.3) and 0.0430, respectively. The AAT was higher in smokers compared with the control group, even though it did not reach a significant level (7.039 ± 093 vs. 4.465 ± 0.3901). We did not record any correlation between the measured parameters and packs/year of smokers. Conclusion: In conclusion, our results confirmed the possibility of using AAT, TNF-α and MMP-9 in the early diagnosis of immune system alterations associated with smoking. Understanding the mechanisms behind the development of chronic inflammatory disease would help in the prevention of complications and enable the discovery of therapeutic agents.