Background:This study aimed to assess the serum serotonin levels in the newly diagnosed fibromyalgia (FM) and to relate these levels to the presenting signs and symptoms.Materials and Methods:This case–control study included 35 healthy women (Group I) served as controls and 130 women with newly diagnosed FM (Group II). The diagnosis of FM was confirmed by the diagnostic criteria of the American College of Rheumatology-10. The assessment of pain using a revised fibromyalgia impact questionnaire and tender points scoring, blood platelet indices, and serum serotonin levels were determined.Results:Group II patients had significantly (P < 0.001) higher values of mean platelet volume (MPV) (10.60 ± 1.57fL) and platelet width distribution (16.25 ± 1.45%) than the corresponding values in Group I (8.73 ± 0.81fL and 15.0 ± 1.15%). Significant low-serum serotonin levels observed in Group II patients compared with Group I healthy individuals (187.3 ± 50.3 ng/ml vs. 219.5 ± 78.3 ng/ml, P = 0.026). Multiple linear regression analysis showed the nonsignificant correlations between serum serotonin levels and platelet indices in Group II patients.Conclusion:Newly diagnosed FM women have significantly low-serum serotonin levels, which does not correlate with a significant increment of the platelet activity expressed as increase MPV and platelet width distribution percentage. Therefore, this study highlighted that the correction of serum serotonin level by medicines could help the patients.