Ruiz was among a number of new faces named in Luis Enrique's squad but has now been replaced by Atletico midfielder Saul, who was not included in the original 23-man party.
Getafe striker Jaime Mata and Real Betis midfielder Sergio Canales have been handed their first call-ups to the international stage. Sevilla defender Sergi Gomez is also in line for their first Spain caps after being included, while Valencia midfielder Dani Parejo and Espanyol central defender Mario Hermoso will be hoping to earn their second appearances.
One notable absentee is Isco, who has been left out after dismal last few months at Real Madrid which saw him slip way down the pecking order at the club under Santiago Solari.
Zinedine Zidane was re-appointed at Santiago Bernabeu in Solari's stead on Monday and he is expected to restore Isco to the first team, but he has not seen enough playing time recently to make Luis Enrique's final selection.
Saul's Atletico team-mate Koke also failed to make the cut, along with Diego Costa, who is still struggling with fitness issues.
Spain will be hoping to get their European Championship's qualifying campaign off to a good start against Norway on March 23, before making the trip to Malta three days later.
La Roja won the competition in both 2008 and 2012, with a 2010 World Cup triumph wedged in between, but their success has dried up in recent years.
Vincente del Bosque stepped down as head coach after Spain were knocked out of Euro 2016 in the last 16 by Italy, while Fernando Hierro could only guide his country to the same stage at the World Cup two years later.
FULL SPAIN SQUAD FOR MARCH EUROPEAN CHAMPIONSHIP QUALIFIERS:
Goalkeepers: David de Gea, Kepa Arrizabalaga, Pau Lopez.
Defenders: Jose Gaya, Jordi Alba, Juan Bernat, Mario Hermoso, Inigo Martinez, Sergio Ramos, Sergi Gomez, Jesus Navas, Sergi Roberto.
Midfielders: Sergio Busquets, Rodri Hernandez, Dani Ceballos, Saul Niguez, Sergio Canales, Dani Parejo.
Strikers: Alvaro Morata, Rodrigo Moreno, Marco Asensio, Iker Muniain, Jaime Mata.