[1] Pope John Paul II named him Bishop of Orense on 27 December 1996 and he received his episcopal consecration on 22 February 1997[1] from the Apostolic Nuncio to Spain Archbishop Lajos Kada.

[9] Pope Francis announced that he would elevate Osoro Sierra to the rank of cardinal on 19 November 2016, where he was made Cardinal-Priest of Santa Maria in Trastevere.

[12] Pope Francis has referred to Osoro Sierra as "Don Carlos the pilgrim", alluding to the cardinal's frequent walks around his archdiocese during which he mingles with the people to get to know them better.

[11][13] He has made religious vocations one of his chief priorities and in Valencia the number of seminarians grew from 51 in 2012 to 61 in 2013 due to his efforts.

He invites adolescents to join him at the start of each month for a vigil in which to dialogue with them to understand their needs and concerns and he often celebrates Mass in prisons.

[15] Pope Francis named him a member of the Congregation for the Oriental Churches on 6 August 2019[16] and of the Pontifical Commission for Latin America on 10 March 2021.