Objective We aimed to evaluate all-cause and cause-specific mortality in patients with systemic lupus erythematosus (SLE) and neuropsychiatric (NP) symptoms in the Netherlands between 2007–2018. Methods Patients visiting the tertiary referral NPSLE clinic of the Leiden University Medical Center were included. NP symptoms were attributed to SLE requiring treatment (major NPSLE) or to other and mild causes (minor/non-NPSLE). Municipal registries were checked for current status (alive/deceased). Standardized mortality ratios (SMRs) and 95% confidence intervals (CI) were calculated using data from the Dutch population. Rate ratio (RR) and 95% CI were calculated using direct standardization to compare mortality between major NPSLE and minor/non-NPSLE. Results 351 patients were included and 149 patients were classified as major NPSLE (42.5%). Compared with the general population, mortality was increased in major NPSLE (SMR 5.0 (95% CI: 2.6–8.5)) and minor/non-NPSLE patients (SMR 3.7 (95% CI: 2.2–6.0)). Compared with minor/non-NPSLE, mortality was similar in major NPSLE patients (RR: 1.0 (95% CI: 0.5–2.0)). Cause-specific mortality rates demonstrated an increased risk of death due to infections in both groups, whereas death due to cardiovascular disease was only increased in minor/non-NPSLE patients. Conclusion Mortality was increased in both major NPSLE and minor/non-NPSLE patients in comparison with the general population. There was no difference in mortality between major NPSLE and minor/non-NPSLE patients.