Background:  A systemic condition with a very complex pathophysiology is rheumatoid arthritis. It has been discovered that IL-17A has strong pro-inflammatory characteristics. Sirtuin-1 contributes to chronic inflammation, and its levels in chronic inflammatory illnesses are still under investigations. Up to our Knowledge, the relation between such two markers not yet studied in rheumatoid arthritis patients. Objectives: The aim of the current study is to evaluate sirtuin-1 in rheumatoid arthritis patients and analyze the potential association between sirtuin-1 level and serum IL-17A levels and their relations to disease activity. Patients and methods: A cross-sectional study was conducted on 60 Rheumatoid Arthritis (RA) patients and 30 healthy volunteers. Every participant was subjected to history taking, clinical examination, and laboratory evaluation. Results: both IL-17A and sirtuin-1 were substantially more in RA patients and significantly correlated to most of measured variables. IL-17A and sirtuin-1can be diagnostic indicator of RA with sensitivity (96.67% and 96.67%, respectively) and specificity (96.67% and 86.67%, respectively) and can be indicators of high disease activity with sensitivity (90% and 80%, respectively) and specificity (94% and 94%, respectively), while combined sirtuin-1 and IL-17A diagnostic performance adds much to specificity to discriminate those with high active disease; Sirtuin-1 (Coefficient B= 0.249, P<0.006) and IL-17A (Coefficient B= 0.043, P<0.012) were independent predictors of disease activity. Conclusion: Compared to healthy individuals, RA patients had considerably greater levels of IL-17A and sirtuin-1. IL-17A has better sensitivity and specificity than situin-1 in discriminating patients, remission and high disease activity states.  Sirtuin-1 combined with IL-17 is beneficial in improving the discriminative power for high disease activity, therefore, both might be thought of as potential biomarkers for RA disease activity.