AbstractControl of the skin parasitic ciliateIchthyophthirius multifiliisis currently based on laborious chemical and mechanical approaches, thus advocating for alternative control measures. Here, we show that the early development of trophonts (feeding stage residing in the epidermis) in the Rainbow TroutOncorhynchus mykissepidermis was inhibited at 5 d postinfection after the administration of feed additives, including garlicAllium sativum, oreganoOriganum onites, thymeThymus vulgaris, corianderCoriandrum sativum, and astaxanthin (a carotenoid derived from the algaHaematococcus pluvialis). However, no inhibition was observed at 8 d postinfection. We investigated whether the early inhibition was caused by (1) the feed additives’ direct effect on the parasite and/or (2) stimulation of the Rainbow Trout immune responses. Garlic exhibited the highest in vitro killing capacity toward theronts (the infective stage of the parasite), followed by oregano, thyme, and astaxanthin, whereas coriander had no in vitro parasiticidal effect. Immune reactions were measured by plasma lysozyme activity in Rainbow Trout after feeding and by recording immune gene expression in trout leukocytes that were exposed to feed additives. Oregano‐fed fish showed a significantly (P < 0.05) elevated plasma lysozyme activity. Oregano and thyme—and to a lesser extent, garlic, astaxanthin, and coriander—induced a significant regulation of innate and adaptive immune genes in vitro. The results suggest that the investigated additives inhibit early parasite development directly as well as indirectly (i.e., by elevating the host immune response).