BACKGROUND: Systemic lupus erythematosus (SLE) can affect multiple organs or systems. The involvement of the central nervous system can result in the manifestation of epilepsy, an acute confusional state, and other rare neuropsychiatric presentations, such as catatonia. CASE SUMMARY: We present a case of an adolescent male patient with first-onset SLE who presented with neuropsychiatric symptoms including epilepsy and delirium. The initial utilization of olanzapine to alleviate symptoms of agitation precipitated the emergence of catatonia, which was mitigated by discontinuing olanzapine and supplementing with lorazepam. In this case, whether the catatonia was secondary to the utilization of antipsychotics or to an organic disease is a question that warrants differential diagnosis. CONCLUSION: Multidisciplinary collaborative management is the cornerstone for the successful management of severe cases of SLE.