Toll-like receptor (TLR) activation and cytokines have been linked to the disease flare of systemic lupus erythematosus (SLE), yet the expression profiles of TLRs and cytokines in response to TLR activation in SLE patients remain unclear. In this study, we evaluated the expression levels of IL-10, TNF-α, interferon-γ (IFN-γ), TLR-2, TLR-4, and TLR-9 in peripheral blood mononuclear cells (PBMCs) from SLE patients and normal controls after PBMCs were stimulated with a TLR-2, TLR-4, or TLR-9 agonist. The expression levels in SLE patient group were statistically compared with those in normal control group. It was found in SLE patients that the IL-10 protein production was down-regulated after the activation of TLR-2, TLR-4, or TLR-9 and that the TNF-α protein production was decreased after the activation of TLR-2 or TLR-9, but not TLR-4. However, the transcript levels of IL-10 and TNF-α as well as the protein and transcript levels of IFN-γ were comparable between SLE and normal control groups. In addition, the TLR-2 transcript levels seem to be diminished after the activation of TLR-2, TLR-4, or TLR-9, but TLR-4 and TLR-9 transcript levels were not altered. The results indicate that the cytokine production from PBMCs in response to TLR activation is dysregulated in SLE patients, supporting the possibility that TLR activation may influence lupus disease activity through regulating cytokine production.