Background: Rheumatoid arthritis (RA) is a chronic systemic inflammatory disorder which mainly affects small joints, occurs most commonly in middle-aged adults, and can be fatal in severe cases. The exact etiology of RA remains unknown. However, uncontrolled expression of pro-inflammatory cytokines and chemokines can contribute to the pathogenesis of RA. Aim: In the current study, we assessed the potential of serum concentrations of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, IL-8, and C-C motif chemokine ligand (CCL)5 as early predictive markers for RA. Methods: In addition to clinical examination, blood samples were collected from 100 Saudi patients recently diagnosed with early RA for basic and serological tests, including rheumatoid factor (RF), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). Sera of 32 healthy individuals were used as controls. Specific enzyme-linked immunosorbent assay was used to quantify the serum IL-1β, IL-6, TNF-α, IL-8, and CCL5 levels in the samples. Results: Our results indicated that RF, CRP, and ESR levels were higher in RA patients compared to controls. Furthermore, serum levels of IL-1β, IL-6, IL-8, and CCL5, but not TNF-α, significantly increased in RA patients compared to controls. Conclusion: Overall, the findings suggested that IL-1β, IL-6, IL-8, and CCL5 can be used as biomarkers in the early diagnosis of RA.