The Sea of Marmara is an inland sea connecting world’s two oceanographically distinct seas, the Black Sea and the Mediterranean Sea. The seasonally collected bacterioplankton data were compared using 16S rRNA sequencing technique. The alpha and gamma Proteobacteria groups were the most abundant groups among the cultivable species in the area. The lower layer waters of the Sea of Marmara had the highest variations of isolates and 57% of them were below 100 m, whereas 42% was below 350 m and 16% were below 1000 m. Although the physical parameters remained constant below 350 m, the biochemical parameters including the nutrients and dissolved oxygen varied greatly which might have played important role on the variations of the species composition. Comparison between seasons showed that the highest diversity at the upper layer was obtained in March 2006, following a spring phytoplankton bloom where the carbon concentrations significantly increased. These data clearly showed that the bacterioplankton species in the Sea of Marmara vary both in temporal and spatial scale, mostly driven by environmental conditions.