Study objectives. To assess serum amyloid alpha (SAA) pleural fluid levels in parapneumonic effusion (PPE) and to investigate SAA diagnostic performance in PPE diagnosis and outcome.Methods. We studied prospectively 57 consecutive patients with PPE (empyema (EMP), complicated (CPE), and uncomplicated parapneumonic effusion (UPE)). SAA, CRP, TNF-α, IL-1β, and IL-6 levels were evaluated in serum and pleural fluid at baseline. Patients were followed for 6-months to detect pleural thickening/loculations.Results. Pleural SAA levels (mg/dL) median(IQR) were significantly higher in CPE compared to UPE (P<0.04); CRP levels were higher in EMP and CPE compared to UPE (P<0.01). There was no significant difference between IL-1β, IL-6, TNF-α level in different PPE forms. No significant association between SAA levels and 6-month outcome was found. At 6-months, patients with no evidence of loculations/thickening had significantly higher pleural fluid pH, glucose levels (P=0.03), lower LDH (P=0.005), IL-1β levels (P=0.001) compared to patients who presented pleural loculations/thickening.Conclusions. SAA is increased in complicated PPE, and it might be useful as a biomarker for UPE and CPE diagnosis. SAA levels did not demonstrate considerable diagnostic performance in identifying patients who develop pleural thickening/loculations after a PPE.