Objective: The study aimed to determine the salivary levels of C reactive Protein (CRP), Procalcitonin (PCT), and Matrixmetalloproteinase-8(MMP-8) in periodontitis patients and compare these levels between smokers and non-smokers.Methods: Eighty male subjects aged 25-60 years were chosen and divided into four groups, each comprising 20 individuals: group I: non-smokers without periodontitis, group II: smokers without periodontitis, group III: non-smokers with periodontitis, and group IV: smokers with periodontitis, based on their smoking habit and clinical periodontal parameters which included plaque index (PI%), bleeding index (BI%), pocket probing depth (PPD) and clinical attachment loss (CAL). To assess the salivary concentration, enzyme-linked immunosorbent assay (ELISA) was used for PCT, CRP, and MMP-8, IBM SPSS program version 22 was used for analysis, while ANOVA and Kruskal-Wallis test were used to compare the means and medians in normally distributed and non-normally distributed variables, respectively.Results: There were significant variations in the clinical variables PI, BI, PPD, and CAL between the test and control groups (P<0.05). Furthermore, significant differences were detected in the levels of biomarkers PCT, CRP, and MMP-8 among the four groups. Also, a significant difference was recorded between the levels of these biomarkers and smoking (P<0.05).Conclusions: The study found higher levels of salivary biomarkers in periodontitis and smoker individuals compared to non-periodontitis and non-smoker individuals.