The diversity-disease hypothesis states that decreased genetic diversity in host populations increases the incidence of diseases caused by pathogens (= monoculture effect) and eventually influences ecosystem functioning. The monoculture effect is well-known from crop studies and may be partially specific to the artificial situation in agriculture. The effect received little attention in animal populations of different diversities. Compared with plants, animals are mobile and exhibiting social interactions. We followed the spread of a microsporidian parasite in semi-natural outdoor Daphnia magna populations of low and high genetic diversity. We used randomly selected, naturally occurring host genotypes. Host populations of low diversity were initially monoclonal, while the host populations of high diversity started with 10 genotypes per replicate. We found that the parasite spread significantly better in host populations of low diversity compared with host populations of high diversity, independent of parasite diversity. The difference was visible over a 3-year period. Host genotypic diversity did not affect host population density. Our experiment demonstrated a monoculture effect in independently replicated semi-natural zooplankton populations, indicating that the monoculture effect may be relevant beyond agriculture.