Synergistic epistasis for fitness is often assumed in models of how selection acts on the frequency and distribution of deleterious mutations. Evidence for synergistic epistasis would exist if the logarithm of fitness declines more quickly with number of deleterious mutations, than predicted by a linear decline. This can be studied indirectly by quantifying the effect of different levels of inbreeding on fitness. Here, six sets (different genetic backgrounds) of three increasingly inbred Daphnia magna clones were used to assess their relative fitness according to changes in frequency in a competition experiment against a tester clone. A novelty of the mating procedure was that the inbreeding coefficients (F) of the three clones belonging to each set increased in steps of 0.25 independent of the (unknown) inbreeding coefficient of the common ancestor. The equal increase of the inbreeding coefficients is important, because deviations influence the quantification of inbreeding depression, its variance and the detection of epistasis. In a simple mathematical model we show that when working with a partially inbred population inbreeding depression is underestimated, the variance of fitness is increased, and the detection of epistasis more difficult. Further, to examine whether an interaction between inbreeding and parasitism exists, each inbred clone was tested with and without a microsporidium infection (Octosporea bayeri). We found a nonlinear decrease of the logarithm of fitness across the three levels of inbreeding, indicating synergistic epistasis. The interaction term between parasitism and inbreeding was not significant. Our results suggest that deleterious mutations may be purged effectively once the level of inbreeding is high, but that parasitism seems not to influence this effect.