Purpose Chronic pelvic pain syndrome (CPPS) is permanent pelvic pain of unknown etiology. Current theories suggest a multifactorial origin for CPPS, including urinary pathologies, psychosocial factors, prostate inflammation, infection, central sensitization of the nervous system, and muscular contractures or fibrosis. As there are no defined treatment protocols for CPPS, a multimodal approach is recommended. The objective of this study was to evaluate the impact of a manual therapy treatment protocol on pain, urinary symptoms, and overall quality of life. Materials and Methods Twenty-three men aged 47.36 ± 10.11 years were recruited consecutively by urologists practicing at two hospitals. All men presented prostatic tenderness with no other positive clinical history, urine cultures, or echography studies. Patients underwent six manual therapy sessions (three during the first week and three every two weeks after that) performed by a single osteopath or physiotherapist. The intervention protocol addressed the treatment of muscle structures, fascial mechanics, vascularization, innervation, emotional factors, and the need for information. The questionnaires used to evaluate outcomes included the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI), the International Prostate Symptoms Score (IPSS), and a Visual Analog Scale (VAS) for pain, and the Hospital Anxiety and Depression Scale (HADS). Data were evaluated using Chi-squared or paired difference tests by an external researcher. Results The mean NIH-CPSI scores recorded for our study cohort decreased by 7.69 points (30.92%; <0.0005; 95% CI 4.02-10.52). IPSS measurements decreased by 3.20 points (22.18%; =0.009; 95% CI 1.00-6.09), although the item addressing quality of life decreased by 1.67 points only (31.99%; <0.0005; 95% CI 0.94-2.33). The VAS score also decreased by 2.20 points (38.6%; <0.0005; 95% CI 1.45-2.73). Changes in HADS scores were not statistically significant. Conclusions Based on patient responses, this case series revealed that manual therapy improved urinary symptoms, pain, and quality of life.