Objectives: Immunocompromised patients infected with SARS-CoV-2 have been shown to shed replicable virus for a prolonged period of time, and the duration of isolation can therefore be difficult to estimate. The objective of this study was to evaluate the viral load dynamic in non-hospitalized immunocompromised patients infected with SARS-CoV-2 and treated with monoclonal antibodies (mAbs) or antivirals. Methods: Oropharyngeal swabs for RT-PCR and viral culture were collected from 29 immunocompromised patients before treatment with mAbs or antivirals and at days 5 and 15 after treatment. Overall, 12 patients were infected with the subvariant Omicron BA.1, 12 with Omicron BA.2, two with the Delta variant and for three patients determination of the variant were inconclusive. Results: Before treatment with mAbs or antivirals, 22 of 29 patients (76% [95% CI, 56–90]) shed replicative SARS-CoV-2. At day 5, 21 patients (72% [95% CI, 53–87]) still tested RT-PCR–positive, but for 14 patients (48% [95% CI, 29–67]) there were no replicative virus in culture. At day 15, 16 patients (55% [95% CI, 36–74%]) tested positive but only two patients (7% [95%CI, 1–23]) had replicative virus. Discussion: Half of the patients in this cohort had no viable virus after 5 days and only two patients had replicative virus after 15 days. This could indicate that the current CDC recommendations of an isolation period of 20 days for immunocompromised patients infected with SARS-CoV-2 could be reduced, but larger studies are needed to estimate the isolation duration for immunocompromised patients.