['To investigate if lymphopenia is associated with clinical manifestations, disease activity and prognosis in systemic lupus erythematosus (SLE).', 'The charts of 186 paediatric patients with SLE diagnosed between 1985 and 2006 in a medical centre were retrospectively reviewed. Lymphocyte counts were recorded at the time of SLE diagnosis and SLE flares. Global disease activity was quantified by the SLE Disease Activity Index (SLEDAI). Cumulative organ damage was assessed by the ACR/Systemic Lupus International Collaborating Clinics (SLICC) damage index.', 'Lymphopenia (<1500/mm(3)) and marked lymphopenia (<500/mm(3)) was observed in 62.8 and 12.2% at the time of SLE diagnosis. At the time of SLE diagnosis, lymphopenia was significantly associated with oral ulcers, leucopenia, anti-dsDNA antibodies and C4 decrease. At the time of flares, lymphopenia was significantly associated with anti-dsDNA antibodies, methylprednisolone pulse therapy, disease activity and organ damage. Using multivariate logistic regression, marked lymphopenia was independently associated with neuropsychiatric manifestations [odds ratio (OR) 7.41, 95% confidence interval (CI) 1.99-27.0], and protective from LN (OR 0.13, 95% CI 0.03-0.53).'] Is lymphopenia associated with neuropsychiatric manifestations and disease activity in paediatric systemic lupus erythematosus patients?