Fibromyalgia (FM) is a complex pain condition where the pathophysiological and molecular mechanisms are not fully elucidated. The primary aim of this study was to investigate the plasma proteome profile in women with FM compared to controls. The secondary aim was to investigate if plasma protein patterns correlate with the clinical variables pain intensity, sensitivity, and psychological distress. Clinical variables/background data were retrieved through questionnaires. Pressure pain thresholds (PPT) were assessed using an algometer. The plasma proteome profile of FM (n = 30) and controls (n = 32) was analyzed using two-dimensional gel electrophoresis and mass spectrometry. Quantified proteins were analyzed regarding group differences, and correlations to clinical parameters in FM, using multivariate statistics. Clear significant differences between FM and controls were found in proteins involved in inflammatory, metabolic, and immunity processes. Pain intensity, PPT, and psychological distress in FM had associations with specific plasma proteins involved in blood coagulation, metabolic, inflammation and immunity processes. This study further confirms that systemic differences in protein expression exist in women with FM compared to controls and that altered levels of specific plasma proteins are associated with different clinical parameters.