This study reports on the predictive relationship between serological, immunological and pathological responses following experimental inoculation with incremental doses of Fasciola gigantica in sheep. Fifty, 6-month-old, naive Merino wethers were allocated to one of 5 experimental groups, four of which received 50, 125, 225 and 400 metacercariae, respectively, whilst a 5th group acted as non-inoculated control. Strong individual correlations were observed between liver score, GLDH (glutamate dehydrogenase), GGT (gamma glutamyl transferase), CatL5 (cathepsin L5) antibody titre (IgG1, IgA), eosinophilia, and the total worm count or worm biomass. A combination of multiple indicator traits performed significantly better than any single indicator trait alone. The best predictive index accounted for up to 88% of observed worm burden (Wb) if information on inoculation dose was available. Without knowledge of inoculation dose, such as under field conditions, up to 67% of variation in worm burden could be predicted. In contrast, the best single predictor variable (liver damage score) accounted for up to 50% of worm burden, and in the absence of post-slaughter information, serum levels of anti-cathepsin IgA antibody titres accounted for 35% of predicted variation in worm burden. The utility of a predictive index under both field and experimental inoculation conditions is discussed.