The red imported fire ant, Solenopsis invicta Buren, is a serious agricultural, ecological, and public health pest in its invaded range. Chemical insecticides have been widely used for the prevention and control of this notorious pest. To search for novel, cost-effective, and environmentally friendly materials for fire ant control, we tested various sweeteners for their toxicity to S. invicta. The S. invicta that were fed erythritol, aspartame, and saccharin exhibited significantly higher mortality rates than those fed other sweeteners. After 72 h, the mortality of the workers that were fed 0.1 or 0.2 g/ml erythritol was above 80%. For males, females, and larvae, mortality was close to 100% after 9 d at high concentrations. Dose-dependent effects of erythritol were observed for workers, males, females, and larvae at the concentrations tested. Rapid transfer of toxicity among the fire ant colony was also observed. Our results suggest that erythritol can be developed as an additive ingredient in baits.