The marine crustacean Lepeophtheirus salmonis (salmon louse) is a common ectoparasite of wild and farmed salmonids. The parasite has a complex ontogeny comprising eight instars. The planktonic copepodid stage settles on host skin and pass through five instars to reach the adult stage. The present study comprises an experimental infestation of Oncorhynchus mykiss (rainbow trout) with salmon lice and describes histopathology and host immune responses in skin beneath the louse at multiple time points encompassing all louse developmental stages. Each fish was exposed to 80 infective copepodids, a mean no. of 32 parasites reached the preadult I stage whereas a mean no. of 11 parasites reached the adult stage. A progression in the severity of cutaneous lesions was observed, and levels of immune gene transcripts at the attachment site revealed a dynamic response, initially related to innate immunity. Later, immune cells accumulated in the dermis concomitant with a moderate decrease in levels of transcripts characteristic of both innate and adaptive immune responses. The present study also demonstrates that the cutaneous immune response was mainly induced at lice affected sites, while non-affected skin resembled the skin of untreated control. This indicates that the skin cannot be regarded as a uniform organ and requires careful sampling at all salmon louse stages.