The group expects around 150,000 faithful will flock to the beatification — the last step before sainthood — of Alvaro del Portillo, who headed Opus Dei from 1975 until his death in 1994.
The ceremony will be presided over by the head of the Vatican department that oversees the making of saints, Cardinal Angelo Amato, aided by 1,300 priests and 300 cardinals, bishops and archbishops.
Although it has its headquarters in Rome, Spain remains one of Opus Dei's strongholds — it has roughly 30,000 members there, representing one third of its 90,000 following.
The beatification comes just 12 years after Pope John Paul II canonized Del Portillo's predecessor Jose Maria Escriva de Balaguer, the Spanish Roman Catholic priest who founded Opus Dei in 1928.
"This event is an obvious show of force on the part of Opus Dei," said the director of religious affairs website Religion Digital, Jose Manuel Vidal.
With Del Portillo's beatification, Opus Dei wants to show "that it is still a force in Spain and the world".
But Vidal and other analysts said Opus Dei is losing followers — who are turned off by its demand that members incorporate a strict routine of prayer, sacrifice and service into their daily lives — and has lost political influence in Spain and at the Vatican.
Opus Dei, which means "God's Work" in Latin, teaches Catholics to strive for holiness through their work and ordinary lives.
It became well-known through Dan Brown's novel "The Da Vinci Code" that portrays it as having a hand in running the world.
In real life, it runs universities, schools and benevolent projects around the world, and offers religious education to young people.
In Spain, Opus Dei set up the top-ranked IESE Business School.
– 'Opus manipulates membership numbers' –
About 20 percent of Opus Dei's members have chosen to remain celibate and donate the bulk of their salaries to the organization.
Many of the more committed members live in communal homes where men and women are segregated.
But Spanish sociologist Alberto Moncada, a former Opus Dei member who has written several books about the group, said Opus Dei "manipulates" its membership figures, which he believes are far lower.
Over the past decade more people have left the group each year than have entered it, he added.
"Opus has become a teaching service for moneyed classes. That is their main objective in the world. They have little or no political influence," he said.
Only one member of Spanish Prime Minister Mariano Rajoy's conservative cabinet, Interior Minister Jorge Fernandez Diaz, belongs to Opus Dei, Moncada said.
By comparison at least three ministers in the previous Popular Party government of Prime Minister Jose Maria Aznar, who ruled from 1996 to 2004, were members of the group at one point, according to Vidal.
Opus Dei members also played a key role in developing Spain's economic policy in the 1950s and 1960s during the dictatorship of General Francisco Franco.
"Their capacity to influence today is limited," said Juan Gonzalez Bedoya, religious affairs correspondent at centre-left daily newspaper El Pais.
– Waning influence at Vatican –
But Jose Carlos Martin de la Hoz, a prominent Catholic historian and Opus Dei leader, said it was a "mistake" to try to measure the group's influence by merely counting the number of government ministers who are members.
"Saying that so-and-so belongs to Opus Dei is feeding the idea that Opus Dei will direct his work and tell him what he has to do in his government. Opus Dei does not give instructions," he said.
Analysts said the group's influence at the Vatican has also waned.
Opus Dei's strict adherence to traditional Catholic values, including opposition to artificial contraception, allowed it to flourish under Pope John Paul II, who named one of the group's members as his spokesman.
But these positions run against the spirit of Pope Francis, who has said the Church must end its obsession with teachings on abortion, contraception and homosexuality, and become more merciful.
"Pope Francis has followed a line in the Church that is very different from that which Opus Dei has always defended," said Raquel Mallavibarrena of Christian Networks, a progressive Spanish Catholic association.