Abstract Background Rheumatoid arthritis (RA) is an autoimmune condition characterised by inflamed joints. Disease-modifying anti-rheumatic drugs (DMARD) are ineffective in 30–40% of patients. CD169 (Siglec-1) is expressed by monocytes and correlates with disease activity in RA. It drives pro-inflammatory processes including the suppression of Tregs through its cognate ligand, CD169L. This study aims to define the relationship between CD169, CD169L and disease activity, as a potential early biomarker of treatment response. Methods Peripheral blood mononuclear cells were isolated from healthy controls and RA patients who failed DMARD treatment. FACS was used to: (i) immunophenotype CD169+ monocytes and CD169L+ Tregs, and (ii) assess levels of FoxP3 within Tregs. Results RA patients had a significantly higher percentage of CD169+ monocytes (28.47 ± 7.17, (mean ± SEM), n=19) compared to healthy controls (8.03 ± 1.48, n=19, p=<0.01). A negative correlation was also observed between the percentage of CD169+ monocytes and CD169L+ Tregs in RA patients (r=−0.72, n=19, p=<0.01). Furthermore, the ratio of CD169:CD169L percentages has a positive association with DAS28-ESR (r=0.77, n=9, p=0.02). FoxP3 is expressed at lower levels in RA patients (24.14 ± 1.87, n=25) compared with healthy controls (46.65 ± 6.16, n=13, p=<0.01). Conclusion These results provide preliminary evidence of a relationship between CD169 and CD169L, and further define how their balance is associated with disease activity. Low levels of FoxP3 in RA patients indicates reduced Treg activation, which may cause increased disease activity. We postulate that this balance of cells is key in the immune response and could be used as a surrogate measure of disease activity.