Copepods dominate the biomass of marine zooplankton and through their prey selection they act as top-down regulators of planktonic communities. We investigated feeding preference of copepods in the presence of the diatom Skeletonema marinoi at different time points throughout the development of a bloom and a culture. Quantitative PCR gut content assessment revealed that the food uptake of the copepod Calanus spp. on mixed diets and on artificially induced mesocosm blooms was selective. Uptake of S. marinoi was highest during the post-bloom phase in the mesocosms even if the abundance of this alga was already low. In laboratory assays, copepods showed a greater preference for S. marinoi in the late stationary phase than for cultures of the same strain under exponentially growing culture conditions. The copepods thus discriminate between different growth phases of a single algal species in both laboratory and field settings. In parallel, we monitored cellular metabolites of the diatom using a metabolomic approach. Complex changes in the metabolic profile occur during development of a culture. Since no obvious effect of nutrient quality and cell size was involved, we suggest that changes in (info)chemicals within or surrounding S. marinoi regulate selective feeding by zooplankton.