Axial spondyloarthritis (axSpA) is a chronic multifactorial inflammatory disease of the axial skeleton with activation of innate immunity evidencing by an increase in classical monocytes (cMo) and the dominance of a pro-inflammatory phenotype. However, the immunosuppressive/anti-inflammatory potential of monocyte/macrophages remains practically unexplored. This study aimed to evaluate the expression of tyrosine kinase Mer (MerTK) and arginase 1 (Arg1) in patient monocyte subsets, addressing different clinical features, disease activity, and medication response. Fourty axSpA patients, ranging in age from 22 to 61, and 17 healthy donors, ranging in age from 25 to 58, were enrolled in the study. We have identified the changes in the Mo subsets in axSpA manifested by an increased proportion of cMo and an elevated Mo/Lymphocyte ratio, which are correlated with disease activity. In both donors and patients, MerTK+ and Arg1+ cells were identified in all Mo subsets, with a higher rate in intermediate (iMo) and non-classical (nMo) Mo. However, patient monocytes demonstrated a decreased percentage of MerTK+ cells in nMo and Arg1+ cells within iMo and nMo. The most pronounced decrease in monocyte expression of MerTK and Arg1 was characteristic of a more aggressive course of the disease, including patients with the involvement of peripheral joints (especially with coxitis), positive for HLA-B27, and high disease activity. This data suggests an important role of MerTK and Arg1 in limiting myeloid-driven inflammation and indicates the potential prognostic significance of these molecules as new biomarkers in axSpA.