The high content in nutrients of freshwater outflows induces highly productive and buoyant plumes spreading over marine waters (MW). As a consequence, the growth of organisms developing in these low-salinity waters (LSW) might be potentially affected by UV-R (280–400 nm). This study investigated the penetration of UV-R and its impact on net community production (NCP) and bacterial protein (BPROTS) and DNA (BDNAS) synthesis in mesotrophic-LSW formed from the Rhône River and in oligotrophic MW of the Northwestern Mediterranean Sea (Gulf of Lions) in May 2006. High concentrations of chlorophyll a (up to 8 μg L−1) measured in the LSW (<37.8 psu, 0–10 m) were the main factor influencing the diffuse attenuation coefficients (Kd) of both UV-R and photosynthetically active radiation (PAR). The mean ratio of the Kd measured between the LSW and the MW increased with wavelength from 2.4 at 305 nm to 2.9 at 380 nm and 3.1 for PAR indicating more similarity in the UV region. NCP was severely inhibited by UV-R at the surface of the LSW, whereas no effect was measured in the surrounding MW. In contrast, BPROTS and BDNAS were affected deeper by UV-R in the MW (up to 8 m depth) compared to the LSW where inhibition was only observed at the surface. Differences in response of bacteria in LSW and MW are largely explained by differences in UV-R transparency; however, transplant experiments indicate that bacterial assemblages from the MW were also more sensitive to UV-R than those present in the LSW. We also observed that higher activity of bacteria after nutrient additions increased their sensitivity to UV-R during the day, but favored their recovery during the night incubation period for both LSW and MW. Results suggest that riverine and nutrient inputs may alter the effects of UV-R on microbial activity by attenuating the UV-R penetration and by modifying the physiology of bacteria.