Objectives To study the association of different components of physical fitness [flexibility, muscle strength and cardiorespiratory fitness (CRF)] and a clustered fitness score with health related quality of life (HRQoL) in women with systemic lupus erythematosus (SLE) and to analyze whether participants with high fitness level have better HRQoL. Methods This cross-sectional study included 70 women with SLE (aged 42.5; SD 13.9 years). The back-scratch test assessed flexibility, the 30-sec chair stand and handgrip strength tests assessed muscle strength, and the 6-min walk test (n = 49) assessed CRF. HRQoL was assessed through the 36-item Short-Form Health Survey (SF-36). Results Flexibility was positively associated with the physical function dimension and the physical component summary (PCS) (r(partial) between 0.26 and 0.31; p<0.05), and negatively related with social functioning dimension (r(partial) = -0.26; p<0.05). Muscle strength was positively associated with the physical function, physical role, bodily pain dimensions and the PCS (r(partial) between 0.27 and 0.49; all p<0.05). CRF was positively associated with the physical function and bodily pain dimensions, and PCS (r(partial) between 0.39 and 0.65; all p<0.05). The clustered fitness score was associated with the physical function (B = 17.16) and bodily pain (B = 14.35) dimensions, and the PCS (B = 6.02), all p<0.005. Patients with high fitness level had greater scores in the physical function, physical role, and bodily pain dimensions and the PCS, all p <= 0.05. Conclusions Our study suggests that muscle strength and CRF are positively associated with HRQoL, while flexibility showed contradictory results. These findings highlight the importance of maintaining adequate fitness levels in women with SLE.