The Hotel Saratoga, a luxury 96-room residence in Old Havana, was finishing renovations when an apparent gas leak produced a massive explosion on Friday.
The Saratoga's facade was sheared off, burying workers inside and apparently passers-by outside under concrete and twisted metal.
The explosion came in the late morning when the streets and plaza in front of the stately hotel would have been full of pedestrians.
On Saturday evening, Dr Julio Guerra Izquierdo, chief of hospital services at the Ministry of Health, raised the death toll to 27 with 81 people injured.
The dead included four children and a pregnant woman.
Spain's President Pedro Sanchez said via Twitter that a Spanish tourist was among the dead and another Spaniard was seriously injured.
Some 37 people remained hospitalised, according to the Health Ministry.
Earlier on Saturday afternoon, a representative of Grupo de Turismo Gaviota, which owns the hotel, said 13 of its workers remained missing.
Governor Reinaldo Garcia Zapata said on Saturday evening 19 families had reported loved ones missing and rescue efforts would continue.
At least one survivor was found early on Saturday in the shattered ruins.
Authorities said the cause of the explosion was still under investigation, but it was believed to have been caused by a gas leak.
A large crane hoisted a charred gas tanker out of the rubble on Saturday.
The explosion is another blow to the country's crucial tourism industry.
Crews busily worked to clean up the surrounding streets and by late on Saturday, substantial pedestrian traffic had resumed.
Some nearby buildings were also heavily damaged by the explosion that blew out windows and rattled walls.
Even before the COVID-19 pandemic kept tourists away from Cuba, the country was struggling with tightened sanctions imposed by former US president Donald Trump and kept in place by the Biden administration.
Tourism had started to revive somewhat early this year, but the war in Ukraine deflated a boom of Russian visitors, who accounted for almost a third of those arriving in Cuba last year.
