Arctic regions to date experience the most pronounced transformations due to global change. Current hypotheses propose an elevated impact of those environmental changes on the biodiversity, community composition and metabolic processes of species. Influence on ecosystem function and services, particular when invasive or toxigenic harmful species become dominant, can alter processes on smaller and larger scales. Our study focused on the comparison of molecular biodiversity of three planktonic size-fractions (micro-, nano-, picoplankton) in coastal waters of West Greenland and the correlation with environmental parameters. Molecular diversity was assessed via sequencing the 28S rRNA hypervariable D1/D2 region by parallel amplicon sequencing. We showed that biodiversity distribution within the area of Uummannaq Fjord, Vaigat Strait and Disko Bay differed markedly within and among size-fractions. In general, we observed a higher diversity within the picoplankton size fraction compared to the nano- and microplankton. Community composition of all three size fractions correlated to size, silicate and phosphate, chlorophyll a (chl a) and dinophysistoxin (DTX), but each size fraction community also correlated with other and different environmental parameters. We observed a more homogeneous community of the picoplankton across all stations compared to the bigger size classes, despite different environmental conditions of the sampling areas. This might suggest habitat occupation for larger organisms over plasticity, while smaller organisms compensate a lower potential plasticity with higher diversity. The presence of potential harmful algal bloom (HAB) species (such as Alexandrium fundyense, A. ostenfeldii) in the area points out the risk for this vulnerable ecosystem in a changing world.