Introduction: Recent epidemiological data demonstrate that disease flares often occur without apparent cause but there is evidence that certain environmental factors may trigger the disease such UV light, infections, certain hormones, and drugs. Here, we report a case of systemic lupus erythematosus flare with neuropsychiatric manifestations notably lupus encephalitis, lupus headache, movement disorder, mood disorder, anxiety and cardiovascular manifestation as pulmonary embolism triggered by malaria and urinary infection with Escherichia coli in an elderly Malian woman at the "Polyclinique REVIERA" of Bamako that had been successfully treated. Clinical Observation: An 79-year-old Malian female with history of systemic lupus erythematosus currently under azathioprine, arterial hypertension under candesartan, three episodes of erysipelas, chronic gastritis and a recent history of pulmonary embolism was hospitalized to the "Polyclinique REVIERA" of Bamako with a 5-days history an altered level of consciousness, temporospatial disorientation, broca’s aphasia preceded by a 10-days history of nausea, vomiting, anorexia, epigastric pain, pain in joints and fever and a 1-month history of headache developed and persisted despite investigation and treatment associated with insomnia, anxiety, anhedonia, difficulty in concentrating and loss of energy. Neurologic examination was markedly for broca’s aphasia, myoclonia, seizure, and the Glasgow scale was 07/15. Rheumatologic examination revealed pain and tumefaction left elbow joint, but no deformation of the joints. The dermatological examination noted erythematous-squamous placard on 1/3 of the legs, alopecia and intertrigo. The initial SLEDAI score assessment noted a very high activity of diseases with more than 20 points. A diagnosis of systemic lupus erythematosus flare with neuropsychiatric manifestations notably lupus encephalitis, lupus headache, movement disorder, mood disorder, anxiety and cardiovascular manifestation as pulmonary embolism triggered by malaria and urinary infection with Escherichia coli was considered. The treatment with prednisone at a dose of 1 mg per kilogram of body weight a day with 1-year tapering course associated with adjuvant treatments preceded by a bolus of 600 mg of methylprednisone was initiated. Azathiopurine at a dose of 75 mg a day was maintained. Hydroxycloroquine at a dose of 400 mg a day was added. Artesunate 120 mg and imipenem cilastatin 500 mg/500 mg were prescribed and adequately administered. Her anterior medications were continued such candesartan 16 mg and rivaroxaban 10 mg. The fifteenth hospital day SLEDAI score assessment noted a mild activity of diseases with 5 points. The patient was discharged with 2-week follow up visit appointment. Conclusion: Our case highlights the importance of discussing lupus encephalitis in any case of encephalitic syndrome, especially after having ruled out infectious and neoplastic causes.