Same sex marriage is illegal in Cuba, but bride Wendy Iriepa is legally a woman after undergoing one of the first state sanctioned sex changes in 2007.
Her fiance, Ignacio Estrada, is a noted dissident and gay rights activist in Cuba and is also HIV positive.
The couple say the wedding, timed to coincide with Fidel Castro's birthday, is a "gift" for the former leader.
Lesbian, gay, bisexual and transgender (LGBT) people faced official discrimination for many years in Cuba, and in the early days of the revolution many were sent to labour camps to stamp out their "counter-revolutionary" values.
But since taking over from his brother as Cuba's leader, Raul Castro has introduced a series of gay rights reforms, including legalising sex change operations.
Ignacio Estrada
Ms Iriepa underwent her treatment at the National Centre for Sex Education, which is headed by Raul Castro's daughter, Mariela.
"It's wonderful. It will be the first 'gay' wedding in Cuba," Ms Iriepa told the AFP news agency."I don't want this to be seen as a political act. Even if it's a gift to Fidel, I'm not worried about what the government will think."
'Ode to freedom' Mr Estrada said he had always considered himself to be gay but that "with Wendy, it's totally different".
"Today, I don't know what I am - all I know is that I am in love with a woman," he said.
The wedding was "not a provocation", said Mr Estrada, but an acknowledgment of their relationship.
"Our wedding will be an ode to freedom, and the rights of the LGBT community."
Dissident blogger Yoani Sanchez, who will act as witness at the ceremony, said that while the marriage is not technically a gay wedding "it is the closest we have come".
"For one afternoon, a brief afternoon, we are putting our country into the third millennium."
Huge celebrations are taking place held in Cuba to mark Fidel Castro's 85th birthday.
But it remains unclear whether the man who led Cuba for 50 years will be able to attend.
He has rarely been seen in public since handing power to this brother in 2006 after suffering serious illness.
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