During the Covid-19 pandemic, many intensive care unit (ICU) patients received hydroxychloroquine. The primary objective of this study was to assess the effects of hydroxychloroquine according to its plasma concentration in ICU patients. A single-center retrospective study was performed from March to April 2020 in an ICU of a university hospital. All patients admitted to the ICU with confirmed Covid-19 pneumonia and treated with hydroxychloroquine were included. The study compared 17 patients in whom the hydroxychloroquine plasma concentration was in the therapeutic target (on-target) and 12 patients in whom the plasma concentration was below the target (off-target). The follow-up of patients was 15 days. No association was found between hydroxychloroquine plasma concentration and viral load evolution (P = 0.77). There was no significant difference between the two groups for duration of mechanical ventilation, length of ICU stay, in-hospital mortality, and 15-days mortality. These findings indicate that hydroxychloroquine administration for Covid-19 patients hospitalized in ICU is not associated with improved outcomes. Larger multicenter studies are needed to confirm these results.