Hookworms are highly pathogenic nematodes that parasitize a wide range of mammals, including several species of pinnipeds. At Guafo Island, in the Chilean Patagonia, this parasite reaches almost 100% of prevalence and causes mortality in South American fur seal pups. The objective of this study was to evaluate the effects of hookworm (Uncinaria sp.) infection on the host and the population by experimental deworming and periodical health assessments. During the 2013, 2014 and 2015 austral summers, we treated a randomly selected subset of hookworm-infected pups (n=120) with Ivermectin, and compared this treated group to pups with different intensity of infection based on fecal analysis (n=220). Additionally, we performed necropsies on 38 hookworm infected and 20 hookworm free (control) animals. Pups with severe hookworm infection (n=90) had marked declines in growth rate, erythrocytes, packed cell volume, hemoglobin, and total protein over the first two months of the infection (ANOVA, all p values < 0.025). In the 2015 season, pups with higher number of hookworms (n=42) had moderate leukocytosis during the first two weeks of infection but they were leukopenic two weeks later. Ten of these pups died due to hookworm enteritis and bacteremia during the study period. At necropsy these pups had over 600 hookworms in the intestine with numerous parasites deeply embedded in the mucosa and sometimes free in the peritoneal cavity. At histopathology these pups had decreased numbers of T-lymphocytes and MHCII positive leukocytes in the small intestine when compared to controls (Student T test, p ≤ 0.002). Hookworm infection is a major disease in this population significantly affecting the growth and health status of up to a third of the population. The failure of severely infected pups to sustain an inflammatory response apparently facilitates the presentation of hookworm peritoneal penetration and sepsis, leading to pup death.