Microplastics (MP) are defined as synthetic organic pollutants sized <5 mm and have been recorded in various environments worldwide. Due to their small size, they pose a potential risk for many organisms throughout the food web. However, little is known about MP distribution patterns and associated transport mechanisms. Rivers may act as pathways for MP into marine environments. In this study, we investigate the occurrence of MP in the estuary and lower stretch of the second-largest German River, the Weser, representative of a significant interface between fresh water and marine environments. The aim of the study was to enhance the general understanding by providing novel, comprehensive data and suggestions for future studies on estuarine systems. Surface water samples of two different size classes were collected by ship using an on-board filtration system (11-500 µm fraction) and net sampling (500-5000 µm fraction). After a thorough sample preparation, all samples were analysed with Focal Plane Array (FPA) Fourier Transform Infrared (FTIR) spectroscopy and Attenuated Total Reflection (ATR) FTIR spectroscopy in order to obtain information on MP concentrations, polymer composition and size distribution. Our findings show highest concentrations in the 11-500 µm fraction (2.3 × 101 − 9.7 × 103 m−3), with the polymer cluster acrylates/polyurethanes/varnish being dominant. The >500 µm fraction was dominated by polyethylene. Estimated MP concentrations generally increased in the Turbidity Maximum Zone (TMZ) and decreased towards the open sea. This study contributes to the current research by providing novel insights into the MP pollution of the estuary and lower stretch of an important European river and provides implications for future MP monitoring measures.