Chronic prostatitis is a widespread disease of the prostate affecting men’s sexual and reproductive health worldwide. Its leading causes are urogenital tract infections by microorganisms with a prostate tropism. This study aimed to evaluate semen parameters and the factors associated (lifestyle, urogenital infections, and inflammation) with the onset of chronic prostatitis symptoms. This case-control study included seventy-six donors: 30 volunteers with chronic prostatitis and 46 asymptomatic volunteers for urogenital infections as a control group. Sociodemographic, urinary symptoms, pain location, sexual and reproductive health and lifestyle-related variables were collected in a survey. Seminal quality, cytokine levels in semen and serum, and the presence of nineteen microorganisms in the urogenital tract were evaluated. Prostatitis was also associated with poor sperm morphology, more lipoperoxidation of the sperm membrane, and lower serum nitric oxide concentration. In addition, N. gonorrhoeae infection was detected more frequently in semen samples from volunteers with chronic prostatitis. Volunteers with chronic prostatitis report more frequently erectile dysfunction and premature ejaculation, anxiety, depression, and stress compared to the control group. Chronic prostate infections alter the microbiota from the genitourinary tract causing prostatitis, a disease that affects all life areas, including the familiar environment of patients. Chronic prostatitis affects seminal parameters, with a great impact on life quality and sexual and reproductive health. Despite being a relatively unexplored disease, much remains to be clarified regarding its diagnosis and treatment. Alterations in the genitourinary microbiota can favor sexually transmitted infections that produce chronic and systemic inflammation.