Weight loss is a common phenomenon and an independent prognostic factor in amyotrophic lateral sclerosis (ALS). Several potential causal mechanisms, including intrinsic hypermetabolism and deficient food intake, have been discussed. We investigated the influence of fasting serum glucose, cholesterol, and triglyceride levels at time of diagnosis on survival in ALS. Serum cholesterol (LDL, HDL, and LDL/HDL ratio), triglycerides, and glucose were investigated in 488 patients (age of onset = 57.6 ± 12.6 years) in relation to survival and revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALS-FRS) data. High serum levels of both fasting cholesterol and triglycerides had a significantly positive effect on survival (p < 0.05). We found a median prolonged life expectancy by 14 months for patients with serum triglyceride levels above the median of 1.47 mmol/l. The results suggest that the lipid metabolism and the nutritional status of ALS patients are important prognostic factors. These parameters should be thoroughly monitored during the clinical management of these patients. In case of progressive loss of body weight, a diet rich in lipids and calories should be considered. However, the final decision whether a lipid-rich diet should be recommended to ALS patients can only be based on a double-blind placebo-controlled interventional trial. Our results further imply that lipid-lowering drugs, e.g., statins, should be applied carefully in ALS patients although individual risk considerations must be made.