After the COVID-19 pandemic, the omicron variant of the SARS-CoV-2 virus became the dominant lineage in Spain in 2022. Although it possesses a milder pathogenicity than previous variants, it still poses a high risk of causing severe COVID-19 for immunocompromised populations. A systematic review was conducted to assess the burden of COVID-19 in Spain among immunocompromised patients during the omicron predominance (1/04/2022-1/04/2023), using PubMed, Cochrane Library, and EPICOVIDEHA between May and July 2023. The search retrieved 217 articles, of which a total of 5 were included. Upon analysis, it was observed that immunocompromised patients during the omicron lineage predominance continue to exhibit higher rates of hospitalizations, ICU admissions, and mortality compared to the general population affected by COVID-19. Although the pandemic has ended, the risk persists for immunocompromised individuals.