To evaluate the prevalence and impact of cognitive impairment on health-related-quality of life (HRQoL) in patients with systemic lupus erythematosus (SLE) and neuropsychiatric (NP) symptoms. Patients with SLE and NP symptoms referred to the Leiden NPSLE clinic (2007-2019) were included. In a multidisciplinary evaluation, NP symptoms were attributed to SLE (NPSLE: inflammatory, ischemic, or both combined) or other causes. Four cognitive domains were determined: global cognitive function (score 0-30), learning and memory, executive function and complex attention, and psychomotor speed (all T scores). HRQoL was determined using the mental component score and physical component score of the Short Form 36 health survey. The associations between cognition and NPSLE phenotype and cognition and HRQoL were assessed with multiple regression analyses and linear mixed models corrected for confounding and expressed in SDs. A total of 357 patients (86% female, mean age 44 years) were included. Of those 357 patients, 169 had a follow-up visit (median follow-up 11 months). Impairment in global cognitive function was present in 8% of patients, and in all other cognitive domains in ±50%. The most severe impairment (all domains) was seen in patients with a combined NPSLE phenotype. Diffuse cognitive impairment (learning and memory, executive function and complex attention, and psychomotor speed) was most common and was present more often in patients with an inflammatory phenotype. A weak association between cognition and HRQoL was found both cross-sectionally and longitudinally. In general, 1 SD lower scores on the cognitive domains were associated with at most one-fifth SD lower HRQoL. Objective cognitive impairment is common in SLE patients with NP symptoms, but may have a limited influence on HRQoL.