Video footage posted on social media showed what was claimed to be a Russian barracks in the southern city engulfed in a fierce blaze with some claiming the site was being used by the Wagner mercenary group.
Another video showed rescue workers in the ruins with several bodies visible.
The site, a former resort and hotel complex next to a church in the city known as the Hunter’s Halt, was being used as a barracks with most of the casualties apparently in a mess hall when it was hit.
The strike on Melitopol – reportedly with Himars rockets – was one of several overnight on Russian bases. Explosions were also reported overnight in the Russian occupied Crimea including Sevastopol and Simferopol.
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The strike on Melitopol came as all non-critical infrastructure in the Ukrainian port of Odesa was without power after Russia used Iranian-made drones on Saturday to hit two energy facilities, leaving 1.5 million people cut off from electricity.