The objective of this study is to evaluate efficacy and safety of influenza vaccine in systemic lupus erythematosus (SLE) patients. We studied SLE patients and healthy subjects immunised with inactivated influenza vaccine. Efficacy was measured by comparing humoral response to vaccine antigens between groups. Safety was monitored by SLEDAI and serological markers. Subjects attended visits at baseline and on post-vaccination weeks 4 and 12. We enrolled 62 SLE patients and 47 healthy subjects. In post-immunisation week 4, anti-haemagglutinin antibody titres rose in the patient group at least 6.23-fold, compared to 11.90-fold among controls (P < or = 0.05). The seroconversion rate range was 53-56% among patients and 72-85% among controls (P < 0.05 for strains H1N1 and H3N2, NS for strain type B). The seroprotection rate ranged between 62% and 73% and between 90% and 98% in the patient and control group, respectively (P < 0.05). In post-vaccination week 12, the antibody titre was higher at least 3.86-fold in the patient group and 7.65-fold among controls. The seroconversion rate range was 32-40% among patients and 64-70% among controls, while the seroprotection rate ranged between 43% and 50% and between 79% and 94%, respectively (P < 0.005 for three strains). We identified one severe and six mild to moderate SLE exacerbations by week 12. The anti-nuclear antibodies and anti-double-stranded DNA titres grew by post-immunisation week 4 (P < 0.05). The post-vaccination response was weaker in SLE patients compared to healthy subjects. Immunisation did not change underlying disease activity.