The objective of this study was to assess the flukicidal effect of various anthelmintics against naturally occurring infection of Fasciola, in sheep. Fasciola positive female (n=175) of Kajli breed at Livestock Experiment Station, Khizerabad, district Sargodha were randomly assigned to seven groups, including an untreated control group that received normal saline as placebo. The six groups were treated with four anthelmintics alone and in combination. The faecal egg count reduction test (FECRT) was performed to determine the chemotherapeutic efficacy of anthelmintics. The FECRT for the candidate anthelmintics showed significant (P<0.05) reduction in eggs per gram of faeces of treated groups compared to untreated control group. The highest efficacy was found of a combination therapy of oxyclozanide and oxfendazole (97.50%) treated group; whereas, levamisole treated group showed lowest efficiency (65.67%). Time dependent response of each treatment was determined on 7^th, 14^th, 21^st and 28^th days post treatment. In groups treated with combination of drugs, 28^th day while, in groups treated with single drug 21^st day was found the most efficacious time dependent response against natural Fasciola infection. It can be concluded that combination of oxyclozanide and oxfendazole holds potential as part of an integrated management plan for the control of Fasciola in Pakistan.

Key words: Fasciola spp., Oxfendazole, Oxyclozanide, Resistance, Sheep