A different clinical course and pattern of skeletal involvement in peripheral and axial spondyloarthritis (SpA) suggests a distinct pathophysiology of these 2 phenotypic manifestations of SpA. Monocytes, as part of the innate immune system, seem to play an important role in the pathogenesis of SpA, but the exact inflammatory pathways remain to be elucidated. Regulatory T lymphocytes () and Th17 lymphocytes are also known to influence proinflammatory and anti‑inflammatory reactions. The aim of our study was to compare the absolute numbers of monocyte subpopulations, , and Th17 lymphocytes with clinical measures of disease activity in patients with peripheral and axial SpA. We enrolled 21 patients with peripheral SpA and 27 patients with axial SpA diagnosed according to the Assessment of SpondyloArthritis International Society classification criteria, as well as 23 healthy controls. Patients were under 45 years, naïve to synthetic and biological disease‑modifying antirheumatic drugs and without the administration of systemic glucocorticoids. The absolute numbers of classical, intermediate, nonclassical monocytes, , and Th17 in peripheral blood were analyzed. Disease activity was assessed using the Ankylosing Spondylitis Disease Activity Score (ASDAS-CRP), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and Disease Activity Score 28 (DAS28). In patients with SpA, the number of circulating nonclassical monocytes was decreased in comparison with controls. Only in the peripheral SpA group, a significant negative correlation was found between the concentration of nonclassical monocytes and DAS28 and the number of swollen joints. The 3 groups did not differ in terms of the concentrations of classical or intermediate monocytes and or Th17 lymphocytes. Nonclassical monocytes may play a role in induction and perpetuation of peripheral joint inflammation, at least in peripheral SpA, as cells infiltrating the synovium.