Excessive sedation is associated with poor outcome in critically ill acute respiratory distress syndrome (ARDS) patients. Whether this prognostic effect varies among ARDS patients with and without COVID-19 has yet to be determined. We compared the prognostic value of excessive sedation—in terms of delirium, length of stay in intensive care unit (ICU-LOS) and ICU mortality—between COVID-19 and non-COVID-19 critically ill ARDS patients. This was a second analysis of prospectively collected data in four European academic centers pertaining to 101 adult critically ill ARDS patients with and without COVID-19 disease. Depth of sedation (DOS) and delirium were monitored through processed electroencephalogram (EEG) and the Confusion Assessment Method for ICU (CAM-ICU). Our main exposure was excessive sedation and how it relates to the presence of delirium, ICU-LOS and ICU mortality. The criterion for excessive sedation was met in 73 (72.3%) patients; of these, 15 (82.2%) and 58 (69.1%) were in non-COVID-19 and COVID-19 ARDS groups, respectively. The criteria of delirium were met in 44 patients (60.3%). Moreover, excessive sedation was present in 38 (86.4%) patients with delirium (p < 0.001). ICU death was ascertained in 41 out of 101 (41.0%) patients; of these, 37 (90.2%) had excessive sedation (p < 0.001). The distribution of ICU-LOS among excessive-sedated and non-sedated patients was 22 (16−27) vs. 14 (10.5−19.5) days (p < 0.001), respectively. In a multivariable framework, excessive sedation was independently associated with the development of delirium (p = 0.001), increased ICU mortality (p = 0.009) and longer ICU-LOS (p = 0.000), but only in COVID-19 ARDS patients. Independent of age and gender, excessive sedation might represent a risk factor for delirium in COVID-19 ARDS patients. Similarly, excessive sedation shows to be an independent predictor of ICU-LOS and ICU mortality. The use of continuous EEG-based depth of sedation (DOS) monitoring and delirium assessment in critically ill COVID-19 patients is warranted.