The Streptococcus milleri group, which also includes S. anginosus, S. intermedius and S. constellatus, is found in the oropharynx, upper respiratory tract, gastrointestinal tract, and urogenital tract mucosa. Bacteria in the Streptococcus milleri group are associated with bacteremia and abscess formation. Most reports of Streptococcus milleri group (SMG) infection occur in patients with underlying medical conditions. Predisposing factors that have been associated with S. milleri group empyema include mucosal disturbances (sinusitis, periodontal disease, enteric disease), preceding pneumonia, thoracic surgery, malignancy, neurological disease, alcohol abuse, and diabetes mellitus. We report on a 42-year-old man with mental retardation, who suffered from dyspnea and fever that had developed over 14 days. S. constellatus and anaerobic bacterias (Prevotella buccae and Micromonas micros) were cultured. The patient was treated with drainage of pleural effusion and clindamycin and levofloxacin.