In May 2019, he was promoted to the Greensboro Grasshoppers.[4] He did not play in a game in 2020 due to the cancellation of the minor league season because of the COVID-19 pandemic.[5]
In 2021, De Los Santos pitched for the Altoona Curve and Indianapolis Indians, while missing most of the season with a forearm injury.[6] Following the 2021 season, he was eligible for free agency, but re-signed with the Pirates for the 2022 season.[7]
On April 13, 2022, De Los Santos combined with Chase De Jong and Austin Brice to throw a no-hitter for the Indianapolis Indians of the Triple-AInternational League.[8] On May 22, the Pirates selected De Los Santos's contract, promoting him to the major leagues for the first time.[9] He made his MLB debut on May 25.[10] On August 12, De Los Santos was placed on the 60-day injured list with a right shoulder latissimus dorsi muscle strain.[11] In 26 appearances for Pittsburgh in his rookie campaign, De Los Santos registered an 0–3 record and 4.91 ERA with 26 strikeouts and 3 saves in 25+2⁄3 innings pitched.
De Los Santos was optioned to Triple-A Indianapolis to begin the 2023 season.[12] In 22 games for the Pirates, he logged a 3.33 ERA with 18 strikeouts in 24+1⁄3 innings of work. Following the season on November 2, 2023, De Los Santos was removed from the 40–man roster and sent outright to Triple-A Indianapolis.[13] He elected free agency on November 6.[14]
New York Yankees
On November 21, 2023, De Los Santos signed a minor league contract with the New York Yankees organization.[15][16] He made 51 appearances for the Triple–A Scranton/Wilkes-Barre RailRiders in 2024, compiling a 4.12 ERA with 55 strikeouts and 4 saves across 59 innings pitched. On November 3, 2024, the Yankees added De Los Santos to their 40–man roster to prevent him from reaching minor league free agency.[17]
