Negative effects of salmon lice from salmon farms on wild salmonids have been a controversial issue for decades, and concerns are expressed from virtually all areas where salmon farming coexists with important fisheries for wild salmonids. A key question is to what extent lice infestation from farms reduces the number of wild mature salmon returning to spawn in the rivers. Here we study counts and recreational catches of small (< 3 kg), medium-sized (3 – 7 kg), and large mature salmon (> 7 kg) returning to spawn in Norwegian rivers, in association with lice burdens on out-migrating post-smolt recruits. The expected number of returning mature salmon was modelled as a function of theoretical smolt production in the rivers, river catches one generation back in time, size classes of returning salmon, year as a factor, a non-linear spatial effect, and parasite-induced mortality (PIM) of out-migrating post-smolts of salmon. PIM was attributed to small, medium-sized, and large salmon, assuming they spend one (1 SW), two (2 SW), or three winters at sea (3 SW), respectively. There was a significant negative effect of PIM on returns of 1 SW salmon and a negative but non-significant effect on returns of 2 SW salmon. For 3 SW salmon, the effect of PIM was significantly positive, but for comparably low numbers, implying an overall negative effect of PIM on returning salmon. The size-specific effects of PIM were manifested by decreasing proportions of 1 SW salmon in returning populations with increasing PIM, from ~0.6 for rivers exposed to low levels of PIM, to predictions of < 0.2 for rivers exposed to high levels of PIM. This study presents a quantitative relationship between infestations of post-smolt recruits and size-structured returns of mature salmon to Norwegian rivers, suggesting that louse infestation from farms may reduce returns of spawners and restructure the size distribution of mature river populations of Atlantic salmon. The presented relationship opens up for a more targeted approach to obtaining sustainable salmon farming. To accommodate the Norwegian Government’s goal for sustainable aquaculture, reductions in lice abundances in farms are necessary.