The possible role of inflammatory factors in the pathogenesis of restless legs syndrome (RLS) is not well understood. Because several inflammatory diseases have shown an association with the risk for RLS, the measurement of serum/plasma levels of inflammatory factors has been a matter of a scarce number of studies. We performed a systematic review and a meta-analysis to assess the possible association of serum/plasma levels of inflammatory markers with the risk for RLS. Our results showed a significant trend towards higher serum/plasma C reactive protein (CRP) levels and higher neutrophil-to-lymphocyte (NLR) ratio in patients diagnosed with RLS than in controls, although statistical significance disappeared after applying the random-effects model. Further studies are needed to confirm the suggested possible role of inflammatory factors in the pathogenesis of RLS.