The aim of this study was to verify the effect of fasting on the anti-helminthic efficiency of ivermectin-albendazole-levamisole (IAL) combination (first stage) and the closantel and albendazole (second stage) in sheep naturally infected with gastrointestinal nematodes. To this end, fecal samples from young (4 to 6 months), male and female sheep were evaluated seven and 14 days after the treatments, using the Egg count Per Gram of feces (EPG) and the Fecal Egg Count Reduction Test (FECRT). In the first stage of the experiment, the mean EPG of the animals treated and fasted beforehand was lower than the mean EPG of the animals treated, but not fasted 14 days after treatment. Moreover, the group of fasted animals exhibited a better reduction in fecal egg count rate. In the second stage, there was no significant decrease in the mean EPG of the animals in any group (closantel and albendazole) and the efficiency calculated by FECRT was low for the closantel group and zero for the albendazole group. However, the decrease in EPG in animals treated with closantel after fasting was 326.8% greater than the decrease in EPG in animals treated without prior fasting. It was evident that fasting had a positive influence on the reduction of the genera Haemonchus, Cooperia, Trichostrongylus and Oesophagostomum in the animals treated with closantel. The anthelminthic effect of closantel, albendazole and ivermectin-albendazole-levamisole (IAL) combination in sheep was significantly enhanced by previous fasting. Therefore, it is strongly recommended to withhold solid food for a minimum of 12 hours before administering these treatments.