Background: 14-3-3(eta) protein, is an intracellular chaperone (cellular adapter) protein, which released to the extra cellular space during the early stages of the rheumatoid arthritis (RA), and acts as an inducer of innate immune system. Many inflammatory mediators and pathways that involved in the pathogenesis and progression of RA have been upregulated through 14-3-3 eta protein. So, this marker in addition to existing biomarkers can augment the lab efficacy in the early identification and progression assessment of the RA. Objective: Investigating the existence of  anti-CCP antibodies and 14-3-3 protein eta   in juvenile idiopathic arthritis (JIA) and RA patients, comparing that with healthy controls and correlated their levels with Disease Activity Score (DAS 28). Patients and Methods: Serum levels of 14-3-3 eta protein and anti-CCP were measured using enzyme-linked immunosorbent assay (ELISA) in 40 patients including 20 JIA cases (group I), 20 RA cases (group II), and 40 apparently healthy controls. Results: There were highly significant statistical increases in RF, and anti-CCP antibodies in JIA patients as compared with their controls,   while there was insignificant statistical difference between both groups regarding 14-3-3 protein eta.  There were significant statistical increases in14-3-3 protein eta and anti-CCP antibodies in adult RA patients as compared with their controls. In JIA patients, there was significant increase in disease activity score 28 (DAS 28) among patients with +ve RF and +ve anti-CPP, meanwhile there were non-significant relation between DAS 28 and CRP results. Among cases with RA, there was non-significant relation between DAS 28 and the 3 markers (CRP, RF, and anti-CCP antibodies). At cutoff point of 0.19 ng/ml (which was used in many previous studies as the best for 14-3-3 eta protein), our results showed sensitivity and specificity for this marker in JIA (15% and 100%) . In RA, we found 90% sensitivity and 90% specificity for this marker at the same cutoff point. Our study revealed that serum 14-3-3 eta protein level was significantly correlated to disease severity score 28 (DAS 28) for JIA (r = 0.49 / P = 0.0288), while for RA (r = 0.8502 / P= 0.0001). Conclusion: anti-CCP antibodies were prevalent among polyarticular onset JIA patients compared to other subtypes of the disease. 14-3-3 protein had +ve correlation with disease severity in both groups and needs further evaluation on larger samples.