Background: Axial spondyloarthritis (axSpA) is an inflammatory, systemic rheumatic condition that mostly affects the axial skeleton. Tenascin-C (TN-C) is a hexameric glycoprotein of considerable size, upregulated in many inflammatory conditions, while Interleukin-17 (IL-17) a cytokine that plays an important role in SpA symptoms. Objective: to investigate the upregulation between the serum levels of TN-C and IL-17 in Iraqi axSpA patients and the disease characteristics. Patients and Methods: Seventy-four axSpA patients and 28 matched controls were studied. Fifty-four patients received a tumor necrosis factor inhibitor (TNFi) and 20 did not. Serum TN-C and IL-17 concentrations were determined using the ELISA technique. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was assessed. For statistical tests, Chi Square, Mann Whitney, Independent Samples T, and Pearson's correlation tests are used. Results: Patients mean age was 35.6±0.9 years, 65 males and 9 females, and disease duration was 5.18±0.6 years. 47.4% were smokers, 47% had inflammatory low back pain, and HLA-B27 was present in 91%. BASDAI mean was 6.1±0.4 in non-TNFi and 2.6±0.3 in those on TNFi. The serum TN-C concentration was significantly increased in patients, especially those on non-TNFi (79±9.6 pg/mL) compared to those on TNFi (69.1±3.2 pg/mL) and control (53±3.9 pg/mL) (p=0.003). Serum IL-17 was significantly elevated in those receiving TNFi (877.9±257 pg/mL) compared to non-TNFi (487.2±234 pg/mL) and control (182.4±36.6 pg/mL) (p=0.033). The TN-C significantly correlated with erythrocyte sedimentation rate (r=0.27, p=0.02) and with hemoglobin (Hb) concentration (r=0.26, p=0.02). TN-C and IL-17 were non-significantly related (r=0.14, p=0.2). Conclusions: axSpA Patients demonstrated high levels of serum TN-C, particularly in those not receiving TNFi, and high IL-17 levels in those receiving TNFi, suggesting that there is an association with tissue injury from the disease and stimulation of immunological and resident tissue cells. Patients who had not received TNFi showed significantly higher disease activity than others.