We previously reported the peripheral blood cell patterns of expression for the migration inhibitory factor (MIF) canonical (CD74/CD44) and noncanonical receptors (CXCR2, CXCR4, and CXCR7) in rheumatoid arthritis (RA) patients and correlated this with clinical biomarkers and disease activity. This study aimed to evaluate the expression of these receptors alongside the serum levels of CXCL12 and CXCL8 (ligands for CXCR2, CXCR4, and CXCR7), which potentially regulate the action of these receptors and the influence the downstream effects of MIF. Additionally, we evaluated soluble levels of MIF, as well as its soluble cognate receptor (sCD74), in the serum of RA patients and control subjects (CS). Our findings revealed distinctive membrane expression patterns of MIF receptors in active (moderate and high disease activity) and non-active (low activity and remission) RA patients. Furthermore, RA patients exhibited elevated serum sCD74 levels, which correlated with disease activity, and elevated CXCL12 levels, which correlated with rheumatoid factor titers. Regarding serum CXCL8 and MIF levels, we observed higher CXCL8 levels in RA patients compared to CS, while MIF levels did not significantly differ between groups or by disease activity. The circulating sCD74/MIF ratio was elevated in RA patients, particularly in cases of moderate disease activity. Our study also indicated that treatment protocols did not significantly impact circulating MIF levels or the expression of its receptors. This study extends previous findings by supporting a role for sCD74 in downregulating MIF action and in the potential value of the sCD74/MIF ratio as a disease biomarker in RA.