The liver fluke, Fasciola hepatica, is a cause of significant economic losses in sheep farming. Lack of convenient and sensitive diagnostic tests in the live animal hampers the ability to monitor infection status and treatment efficacy. Use of a coproantigen ELISA and coproantigen reduction test, based on this ELISA, may address these issues but has, to date, only been evaluated in experimental challenge studies. We evaluated the coproantigen ELISA under working farm conditions in Scotland to assess its usefulness as a diagnostic test for liver fluke infection and as a diagnostic test to help determine the efficacy of flukicide treatment in sheep. First, liver fluke infection status was monitored longitudinally in a group of lambs, using monthly blood samples for biochemical assays and serum antibody ELISA and using monthly faecal samples for faecal egg count (FEC) and coproantigen ELISA. The average serum antibody ELISA titre became positive in September, two months ahead of faecal indicators of fluke infection. In contrast to results from experimental challenge studies, FEC and coproantigen ELISA became positive at the same time point. Secondly, treatment efficacy was measured in 100 ewes, from two farms, after treatment with triclabendazole (TCBZ) or closantel. Group level estimates of treatment efficacy were similar between faecal egg count reduction testing and coproantigen reduction testing at 7, 14 and 21 days post treatment. For individual animals, some inconsistencies between tests were observed. TCBZ treatment failure was noted on both farms, despite accurate weighing of animals and dosing of treatment products. We conclude that (1) coproantigen ELISA is a more convenient test than faecal egg counts and holds promise as a diagnostic tool for natural fluke infections in sheep but further evaluation of interpretation criteria may be needed; (2) the coproantigen ELISA has performed differently in the field compared with experimental challenge studies in sheep and (3) TCBZ-resistant fluke were present on both farms.