Abstract Background Fibromyalgia syndrome (FMS) is a musculoskeletal disorder characterized by diffuse chronic musculoskeletal pain associated with various other symptoms. Although the etiology and pathogenesis of FMS are still unclear, it was reported to have possible inflammatory basis. No laboratory marker is currently available to diagnose the disease. Aim of the Work to assess the serum levels of ESR, CRP, NLR, MPV and PDW in primary Fibromyalgia syndrome patients and their relation with the disease severity and depression scores. Patients and Methods The study included 30 FMS patients, diagnosed according to the 2010 ACR (American Colleague of Rheumatology) criteria who presented to Ain Shams University Physical Medicine and Rehabilitation clinic as well as 30 healthy volunteers who served as a control group. The following laboratory tests were assessed among both groups: Erythrocyte Sedimentation Rate (ESR), C-reactive protein (CRP), Neutrophil Lymphocyte Ratio (NLR), Mean Platelet Volume (MPV) and Platelet Distribution Width (PDW). FMS patients filled out The Revised Fibromyalgia Impact Questionnaire (FIQR) and Montgomery Asberg Deprssion Score (MADRS) as well. Results MPV, NLR, ESR and CRP values were significantly higher among the patients’ group (p < 0.05). Statistically positive correlation was found between FIQR and each of CRP (p = 0.021) and ESR (p = 0.027) levels. Another statistically significant positive correlation was found between MADRS and CRP (p = 0.01). The NLR showed marginal positive significance with FIQR. Conclusion In the light of these previous results, we can state that the serum levels of the tested inflammatory markers being mainly the acute phase reactants, have a positive relation with disease severity and depression scores, which in turn affect the quality of daily living. Accordingly, we arise the possibility of using those markers as good indicators of ongoing inflammatory process among FMS patients reflecting the severity of the disease.