The zebra mussel (Dreissena polymorpha) provides one example of successful invaders in novel environments. However, little attention has been devoted to exploring the factors regulating zebra mussel density and population size structure at the local scale. We tested effects of physicochemical factors and fish predation on the density of zebra mussels at several sites and between years in a natural lake. Water depth and roach (Rutilus rutilus) density were the most important variables affecting local zebra mussel density. Substrate was also an important factor but affected Dreissena density only at the shallowest depth examined (2 m), which also supported a large population of the mussels. Mean shell length of Dreissena increased with water depth. Our results indicate that predation pressure, intraspecific competition, and food limitation might be responsible for variation in zebra mussel density and population size structure in space and time and that fish predation might have strong top-down effects on zebra mussel populations.