OBJECTIVES To examine the association between a multibiomarker disease activity (MBDA) score, CRP and clinical disease activity measures among RA patients with and without concomitant FM. METHODS In an observational cohort of patients with established RA, we performed a cross-sectional analysis comparing MBDA scores with CRP by rank correlation and cross-classification. MBDA scores, CRP and clinical measures of disease activity were compared between patients with RA alone and RA with concomitant FM (RA and FM) by univariate and multivariate analyses. RESULTS CRP was ⩽1.0 mg/dl for 184 of 198 patients (93%). MBDA scores correlated with CRP (r = 0.755, P < 0.001), but were often discordant, being moderate or high for 19%, 55% and 87% of patients with CRP ⩽0.1, 0.1 to ⩽0.3, or 0.3 to ⩽1.0 mg/dl, respectively. Among patients with CRP ⩽1.0 mg/dl, swollen joint count (SJC) increased linearly across levels of MBDA score, both with (P = 0.021) and without (P = 0.004) adjustment for CRP, whereas CRP was not associated with SJC. The 28-joint-DAS-CRP, other composite measures, and their non-joint-count component measures were significantly greater for patients with RA and FM (n = 25) versus RA alone (n = 173) (all P ⩽ 0.005). MBDA scores and CRP were similar between groups. CONCLUSION MBDA scores frequently indicated RA disease activity when CRP did not. Neither one was significantly greater among patients with RA and FM versus RA alone. Thus, MBDA score may be a useful objective measure for identifying RA patients with active inflammation when CRP is low (⩽1.0 mg/dl), including RA patients with concomitant FM.