The aims of this study are to investigate the cytokine, chemokine and adhesion molecule profiles in cerebrospinal fluid from patients with neuropsychiatric systemic lupus erythematosus and systemic lupus erythematosus with central nervous system infection. Experimental sets were established which included 108 patients and 132 cerebrospinal fluid samples. The patients were grouped as neuropsychiatric systemic lupus erythematosus (n = 54), systemic lupus erythematosus with central nervous system infection (n = 16), systemic lupus erythematosus controls (n=20), and non-inflammatory neurological disease (n=18). The dynamic changes of 21 patients in the neuropsychiatric systemic lupus erythematosus group before and after induction therapy were further analyzed. IL-1 beta, IL-4, IL-6, IL-8, IL-10, IL-12, IL-17, TNFalpha, IFN gamma, IP-10, MCP-1, RANTES, VCAM-1, and P-selectin were measured in cerebrospinal fluid samples by using a fluorescent bead-based assay. Cerebrospinal fluid levels of IL-8, MCP-1, P-selectin and VCAM-1 were significantly increased in neuropsychiatric systemic lupus erythematosus compared with systemic lupus erythematosus controls. IL-6, IL-17, IL-8 and VCAM-1 were higher in systemic lupus erythematosus with central nervous system infection than in systemic lupus erythematosus controls. Among systemic lupus erythematosus with central nervous system infection, the IL-6, IL-17, IL-8 and IP-10 levels were higher than those in neuropsychiatric systemic lupus erythematosus. After sufficient induction therapy, IL-8, MCP-1, P-selectin, VCAM-1 and IL-6 in patients with neuropsychiatric systemic lupus erythematosus decreased significantly. Levels of all molecules tested in non-inflammatory central nervous system disease were not different from those of systemic lupus erythematosus controls. From our data, the intrathecal cytokine/chemokine profile is different among patients with neuropsychiatric systemic lupus erythematosus, systemic lupus erythematosus complicated with central nervous system infection and systemic lupus erythematosus controls. IL-8, MCP-1, VCAM-1, P-selectin and IL-6 in cerebrospinal fluid are effective parameters to monitor neuropsychiatric systemic lupus erythematosus disease activity and response to treatment. Significantly elevated IL-17, IL-6, and to a lesser extent, IL-8, favors central nervous system infection in systemic lupus erythematosus.