To explore the risk of Ureaplasma urealyticum (UU) affecting sperm quality.Prospective cross-sectional study was conducted. In total, 340 semen samples were collected. According to whether they were infected with UU, the samples were divided into the UU-positive group (observation group) and UU-negative group (control group). The patients with UU-positive were followed up to obtain treatment and collected the semen again after treatment. The semen characteristics and sperm parameters were detected and compared, and the relationship of UU and the sperm quality was analyzed by mathematical models.There were 104 UU-positive semen samples in all, with an overall infection rate of 30.6%, which was highest in 31 to 40-year-old men, and over 40-year-old men were the lowest. The pH, PR, VCL, VSL, and STR in the observation group were significantly lower than those in the control group (allP < 0.001), while SV, NP, and WOB were significantly higher (allP < 0.001). After treatment, the pH, VSL, LIN, WOB, and STR in the observation group were significantly higher than before (allP < 0.001), while SV and VCL were significantly lower (allP < 0.001). UU infection was closely correlated with pH, PR, NP, VCL, VSL, WOB, and STR. During the treatment, pH, PR, VSL, WOB, and STR increased, but NP and VCL decreased. 7 major factors that would affect SQ were extracted, of which VAP, LIN, and UU were the first three main factors. The risk of SQ declining after UU infection increased nearly twice with the change of PR and VCL and increased 0.08 times with STR.UU may approximately double the risk of altering the sperm's curvilinear movement rate and straightness to affect the sperm quality.Copyright © 2022 Huang Liu et al.