Ureaplasma urealyticum (U. urealyticum) is a normal commensal that colonizes the human genital tract and usually of low virulence; however, it can trigger serious extragenital infections in immunocompromised patient. In this case, a 48-year-old female immunocompromised patient with a four-year history of recurrent ulcer on extremities was presented to our hospital due to aggravation of lesions 10 months before. She was initially diagnosed as Pseudomonas aeruginosa infection secondary to lupus panniculitis and slightly responded to ceftazidime treatment; however, a new rash appeared on her left hip 16 days after admission, which was aggravated even under antibiotic treatment. After multiple negative cultures, U. urealyticum was identified in her left hip tissue using metagenomic next-generation sequencing (mNGS). U. urealyticum was also confirmed in her secretion samples from left hip, left thigh, right calf and uterine neck using mycoplasma culture and quantitative real-time polymerase chain reaction. Her lesions, especially the new rash, were positively responded to sensitive antibiotic treatment. To the best of our knowledge, this is the first case of U. urealyticum induced recurrent skin and soft-tissue infections (SSTIs) in an immunocompromised adult patient. This case suggests that the prevalence of this kind of infections may be underestimated because of the limitation of routine culture. mNGS may be considered to look for atypical pathogens to improve the antimicrobial treatment of complicated infections.