Since time immemorial, First Nations (FN) communities have incorporated culture into wellness models. Though, empirical support linking enculturation and historical loss with alcohol use is new. The COVID-19 pandemic may trigger pre-existing trauma, as reflected in state affect, thus increasing alcohol misuse risk. Coupling this with growing recognition that cultural connectedness promotes FN peoples’ well-being, the current study assessed the influence of cultural awareness constructs on affect-related alcohol use during the COVID-19 pandemic. We hypothesized that cultural connectedness (CCS), awareness of connectedness (ACS), and historical loss (HLS) would moderate the effect of affect on alcohol outcomes, such that elevated CCS and ACS would mitigate, and HLS exacerbate, the risk of low positive/high negative affect on alcohol outcomes. The current 7-week online study included 48 Anishinabe youth (15-30 years old) who completed baseline measures of CCS, ACS, and HLS and weekly assessments of positive/negative affect and alcohol outcomes. Multi-level Zero-Inflated Poisson (ZIP) regressions supported CCS and ACS as moderators. At high CCS likelihood of alcohol use was mitigated at low positive affect, as hypothesized, but unexpectedly, risk for use was evident at high positive affect. At high ACS, increased positive affect was associated with decreased likelihood of alcohol use, with the opposite found at low ACS, suggesting risk mitigation at high positive affect. As hypothesized, elevated negative affect was associated with reduced negative alcohol consequences, at high (not low) ACS. Results support the protective role of FN youths’ cultural awareness constructs on affective risk for alcohol use in the COVID-19 context.