The 33-year-old Bocanegra, captain since 2007, has lost his starting job with Racing Santander in Spain's second division. He was in the U.S. squad for the 2-1 loss at Honduras last month in the final round of qualifying but didn't play.
With Bocanegra dropped after 110 international appearances and goalkeeper Tim Howard injured, Michael Bradley and Jermaine Jones become the leading candidates to take over as captain.
Eight players are missing from the 23-man squad: Edgar Castillo (triple facial fracture), Timmy Chandler (injured hamstring), Steve Cherundolo (knee surgery), Howard (broke two bones in back), Fabian Johnson (sidelined by hip injury), Jonathan Spector (injured ankle), Jose Torres (injured hamstring) and Danny Williams (stomach virus).
In addition, Landon Donovan remains on an extended offseason break before rejoining the Los Angeles Galaxy in late March.
Clint Dempsey, who has been sidelined by a calf strain since Feb. 21, returned Sunday to play the second half in Tottenham's 1-0 loss to Fulham. Bradley has struggled for playing time of late for Roma and has not completed a full 90 minutes since Feb. 24.
Midfielder DaMarcus Beasley, a veteran of three World Cups, rejoins the team for the first time since a friendly at Mexico last August. Midfielder Brek Shea also was picked despite being limited to two appearances, both as a substitute, since joining Stoke in January.
The injuries leave the U.S. with a makeshift defense for the games against Costa Rica on Friday at Commerce City, Colorado, and March 26 at Mexico City.
Brad Guzan takes over in goal in his first qualifying appearance since 2009. The new central defense tandem of Omar Gonzalez and Geoff Cameron was shaky in the opening qualifier of the 10-team final round, and coach Jurgen Klinsmann has no experienced options for fullbacks.
Just six defenders are in the squad, with Cameron and Gonzalez joined by Tony Beltran, Matt Besler, Clarence Goodson and Justin Morrow. Cameron has played right back for Stoke, and Beasley has played left back at times.
Beltran, Besler and Morrow made their national team debuts during a January friendly against Canada.
Goalkeepers: Brad Guzan (Aston Villa), Sean Johnson (Chicago Fire), Nick Rimando (Real Salt Lake)
Defenders: Tony Beltran (Real Salt Lake), Matt Besler (Sporting Kansas City), Geoff Cameron (Stoke City), Omar Gonzalez (LA Galaxy), Clarence Goodson (Brondby), Justin Morrow (San Jose Earthquakes)
Midfielders: DaMarcus Beasley (Puebla), Kyle Beckerman (Real Salt Lake), Michael Bradley (Roma), Joe Corona (Club Tijuana), Maurice Edu (Bursaspor), Jermaine Jones (Schalke 04), Sacha Kljestan (Anderlecht), Brek Shea (Stoke City), Graham Zusi (Sporting Kansas City)
Forwards: Jozy Altidore (AZ Alkmaar), Terrence Boyd (Rapid Vienna), Clint Dempsey (Tottenham Hotspur), Herculez Gomez (Santos), Eddie Johnson (Seattle Sounders FC)