The 30-year-old, a tourist in 2001, sustained a soft tissue injury in training with Sir Clive Woodward's squad on Friday afternoon, and has been ruled out of the Cardiff outing, along with Scotland back row Simon Taylor (left hamstring).
England's Martin Corry replaces Taylor, also injured in Friday's training, while Munster and Ireland lock Donncha O'Callaghan steps up from the bench for his stricken international compatriot O'Kelly.
Lions assistant coach Ian McGeechan, in charge for Monday's game, said: "We are still awaiting the final assessment on both Malcolm and Simon but with the close proximity of the game on Monday night, changes needed to be put in place."
Further updates on O'Kelly's fitness, currently being monitored by the Lions medical staff, will be issued in due course.
That means three of Leinster's Lions call-ups, Denis Hickie, Gordon D'Arcy and Shane Byrne will start against the Pumas (Monday, May 23 (kick-off 7.45pm, live Sky Sports 1)).
D'Arcy, whose Six Nations campaign was ravaged by a hamstring injury, will form a centre partnership with Leicester and England youngster Ollie Smith, with Lions skipper Brian O'Driscoll being rested.
Also in the backs, Smith's Tigers team mate Geordan Murphy starts in a back three completed by Hickie and Wales flyer Shane Williams.
While England's 2003 World Cup hero Jonny Wilkinson has been given the nod at number 10, up front, Byrne and O'Kelly are joined by Munster's John Hayes, with his provincial colleagues Donncha O'Callaghan and Ronan O'Gara and Leinster's Shane Horgan making the bench.
Wales' Grand Slam-winning skipper Michael Owen will captain the side, with an Ireland (6), England (6) and Wales (3), on his home turf.
The Lions begin their New Zealand odyssey on Saturday, June 4 against the Bay Of Plenty at the Rotorua International stadium (kick-off 8.10am, Irish time).
BRITISH AND IRISH LIONS:
(15) Geordan Murphy (Leicester/Ireland)(14) Denis Hickie (Leinster/Ireland)(13) Ollie Smith (Leicester/England)(12) Gordon D'Arcy (Leinster/Ireland)(11) Shane Williams (Ospreys/Wales)(10) Jonny Wilkinson (Newcastle/England) (Vice Capt)(9) Gareth Cooper (Dragons/Wales)
(16) Steve Thompson (Northampton/England)(17) Julian White (Leicester/England)(18) Ben Kay (Leicester/England)(19) Lawrence Dallaglio (Wasps/England)(20) Chris Cusiter (Borders/Scotland)(21) Ronan O'Gara (Munster/Ireland)(22) Shane Horgan (Leinster/Ireland)
ARGENTINA: Bernardo Stortoni (Bristol); Jose Nunez Piossek (Castres), Felipe Contepomi (Leinster) (Capt), Lisandro Arbizu (Bayonne), Francisco Leonelli (La Tablada); Federico Todeschini (Beziers), Nicolas Fernandez Miranda (Hindu); Mauricio Reggiardo (Castres), Mario Ledesma (Castres), Federico Mendez (Mendoza), Pablo Bouza (Duendes), Mariano Sambucetti (Brive), Federico Genoud (Los Tordos), Martin Schusterman (Plymouth), Juan Manuel Leguizamon (SIC).
Replacements: Eusebio Guinazu (Mendoza), Leopoldo de Chazal (Universidad de Tucuman), Manuel Carizza (Jockey Club Rosario), Santiago Sanz (CASI), Lucio Lopez Fleming (SIC), Francisco Bosch (Hindu), Federico Serra (SIC).
Referee: Stuart Dickinson (Australia)