The fire broke out at 1.34 am in the southern city's Tokyo Star hotel.
Some 65 firefighters backed by 13 emergency vehicles put out the blaze three hours later.
Emergency services said in a statement that eight people died and ten were injured.
Odessa authorities said around 150 people were evacuated from the area.
Police opened a criminal investigation into possible violations of fire safety requirements and the causes of the fire were being established.
Odessa is a Black Sea port 475 kilometres south of Ukraine's capital Kiev. The seaside town also attracts summer tourists.
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