A number of key cabinet ministers are accompanying Fradkov, including Foreign Minister Sergei Lavrov, Economic and Trade Minister German Gref, and Industry and Energy Minister Viktor Khristenko.
A key issue during the talks will be the transit of Russian gas supplies to Europe via Ukraine.
Ukraine, which currently receives Russian gas at subsidized rates in exchange for ensuring transit to Europe, objects strongly to a plan by Moscow to bring Kyiv's payments in line with world market rates.
Russian officials warn the dispute could threaten gas supplies to Europe.
The Brussels talks will focus on bilateral cooperation, visa regulations, and the political situation in Russia, particularly the recent parliamentary elections in Chechnya.