Philip Doyle's side - who beat the Spaniards at the same ground, 16-0 two seasons ago - will boast Blackrock's Germaine Healy in the second row, alongside Rosie Foley - sister of Munster and Ireland number eight Anthony.
That switch sees Healy's club colleague Jen Leacy move to flanker, with Rachel Tucker benched.
Highfield and Munster prop Marie Barrett could also make his first start for Ireland as a substitute. The 30-year-old has put in some sterling work for her province and the Irish Combined Provinces squad this season.
Experienced Cooke centre Suzanne Fleming earns her 37th cap.
WOMENS SIX NATIONS CHAMPIONSHIP: Spain v Ireland, Ciudad Universitaria, Madrid, 2.00pm
SPAIN: M Vila Torrents; M Poza Fernandez, I Etxegibel Alberdi, R Ramirez Arregui, A Obregozo Bereau; AM Aigneren Frodden, I Rodriguez Bergareche (Capt); R Garcia Eiras, A Gonzalez de la Concepcion, A de la Parte Gutierrez, MR Rufino, A Porras Conde, O Garcia Miguel, A Masdeu Anguera, K Alegria Mendaza. Replacements: N Otxoa De Aspuru, M Carreras Espina, R Estanyol Marin, MT Delgado Martinez, M del Mar Perez Martinez, R Socias Olmos, C Ramos Tallada.
IRELAND:
(15) Amanda Greensmith (Shannon) (14) Nuala Ni Chadhain (Galwegians) (13) Suzanne Fleming (Cooke) (12) Patrique Kelly (UL Bohemian) (11) Lynne Cantwell (UL Bohemian) (10) Sarah Jane Belton (UL Bohemian) (Capt) (9) Tania Rosser (Blackrock) (1) Fiona Coughlan (UL Bohemian) (2) Jean Lonergan (Shannon) (3) Edel Coen (UL Bohemian) (4) Rosie Foley (Shannon) (5) Germaine Healy (Blackrock) (6) Rachel Boyd (Cooke) (7) Jean Leacy (Blackrock) (8) Joy Neville (Shannon)
Replacements:
(16) Marie Barrett (Highfield) (17) Emma Stanley (UL Bohemian) (18) Rachel Tucker (UL Bohemian) (19) Orla Brennan (Navan) (20) Louise Beamish (UL Bohemian) (21) Joanne O'Sullivan (Lichfield) (22) Grace Davitt (Boyne)
Head Coach: Philip Doyle Asst Coach: Colin Moran Manager: Mark Andrews Asst Manager: Joy Sparkes Kit Manager: Michael Kelly Physiotherapist: Shirley Real
Referee: Jean-Luc Rebollal (France)
Other results:
Wales Women 0 England Women 81 France Women 22 Scotland Women 15
