The objective of the study was to analyze the impact of TNF antagonists (TNFa) on the total cholesterol and triglycerides on ankylosing spondylitis (AS) and psoriatic arthritis (PsA). In this single-centre observational study of AS and PsA patients, differences in triglyceride and total cholesterol levels and frequency of hypertriglyceridemia and hypercholesterolemia at 3 and 6 months were analysed in patients treated and not treated with TNFa. General estimation equations and linear regression analysis were used to investigate associations between disease activity and lipid levels and to identify predictors of change. One hundred fifty-seven patients treated, and 157 not treated with TNFa, were included in the study. A transient increase in cholesterol level from baseline to 3 months in TNFa-treated patients was the only statistically significant effect (P < 0.001). Persistent percentages of hypertriglyceridemia and hypercholesterolemia from baseline were significantly higher in not treated than in TNFa-treated patients (P = 0.009 and P = 0.001, respectively). Inverse associations between changes in cholesterol level and Bath Ankylosing Spondylitis Disease Activity Index (P = 0.011) and CRP (P < 0.001), but not Disease Activity Score in 28 Joints (P = 0.095) were found in the whole group. In AS and PsA patients treated with TNFa, mild and transient changes in cholesterol but not in triglyceride levels were associated with changes in disease activity.