Fluorosis is a metabolic hard tissue disease caused by ingestion of excessive amount of fluoride mainly through drinking water. We aimed to explore the dose effect correlation among some biochemical indexes of lipid metabolism in fluoride toxicity. Blood samples from 705 patients, age 20–60, with endemic fluorosis living in seven high fluoride (5.9–24.5 mg/L) areas of Punjab, India were examined and compared with 300 matched controls for total cholesterol, high-density lipoproteins (HDL), triglyceride, and low-density lipoproteins (LDL). One-way ANOVA with post Hoc Bonferroni multiple comparison test revealed that the amount of cholesterol declined significantly (P < 0.05 to 0.001) in fluorotic patients of all study groups. The amount of HDL declined significantly (q = 7.07–78.64, 95% CI = –1.32–40.03) in fluorotic patients. A statistically significant (F 7,997 = 1001.8, t = 32.35–61.39, 95%CI = 18.15–40.82, P < 0.05–0.001) accumulation of triglycerides was recorded whereas LDL concentration was reduced significantly (P < 0.001). Bonferroni multiple comparison test revealed that the value of TC/HDL ratio declined significantly (t = 0.19 to 0.56, P < 0.01–0.001) in patients of study groups (5.9–6.5 mg F/L) and subsequently elevated (t = 0.41–2.71, P < 0.05–0.0001) in fluorotic patients exposed to 7.9–24.5 mg F/L. Linear regression and correlation analysis indicated highly significant relationship of serum fluoride with total cholesterol (r = –0.86), HDL (r = –0.90), triglyceride (r = 0.92), LDL (r = –0.55) and TC/HDL ratio (r = 0.74) in fluorotic patients exposed to different levels of fluoride. Fluoride may cause disturbances in lipid metabolism. The decline in the cholesterol content may be due to inhibition of lipid synthesis by fluoride as well as increased utilization of stored lipids as a source of energy to conduct regular metabolic functions.