Urethritis may be caused by the same organisms that cause urinary tract infections (for example, E. coli or klebsiella) and by some sexually transmitted diseases (for example, chlamydia, gonorrhea, and Ureaplasma urealyticum infections). Viral causes of urethritis include herpes simplex virus and cytomegalovirus. Urethritis may also develop because of a chemical irritation (such as spermacide in condoms or contraceptive jelly, cream, or foam). Trauma may also cause urethritis.

Men between the ages of 20 and 35, those with multiple sexual partners, and those who engage in high-risk sexual behavior (such as lack of condom use, particularly during active anal intercourse) are at higher risk.

Young women in their reproductive years are also at risk. In women, common bacterial causes include gonorrhea, chlamydia, mycoplasma hominis, ureaplasma urealyticum, and mycoplasma genitalum. Risk factors include age younger than 20, unmarried status, inner-city population, multiple partners, and a prior history of STDs (sexually transmitted diseases).