Substitutions that fix between SARS-CoV-2 variants can transform the mutational landscape of future evolution via epistasis. For example, large epistatic shifts in mutational effects caused by N501Y underlied the original emergence of Omicron, but whether such epistatic saltations continue to define ongoing SARS-CoV-2 evolution remains unclear. We conducted deep mutational scans to measure the impacts of all single amino acid mutations and single-codon deletions in the spike receptor-binding domain (RBD) on ACE2-binding affinity and protein expression in the recent Omicron BQ.1.1 and XBB.1.5 variants, and we compared mutational patterns to earlier viral strains that we have previously profiled. As with previous deep mutational scans, we find many mutations that are tolerated or even enhance binding to ACE2 receptor. The tolerance of sites to single-codon deletion largely conforms with tolerance to amino acid mutation. Though deletions in the RBD have not yet been seen in dominant lineages, we observe tolerated deletions including at positions that exhibit indel variation across broader sarbecovirus evolution and in emerging SARS-CoV-2 variants of interest, most notably the well-tolerated Δ483 deletion in BA.2.86. The substitutions that distinguish recent viral variants have not induced as dramatic of epistatic perturbations as N501Y, but we identify ongoing epistatic drift in SARS-CoV-2 variants, including interaction between R493Q reversions and mutations at positions 453, 455, and 456, including F456L that defines the XBB.1.5-derived EG.5 lineage. Our results highlight ongoing drift in the effects of mutations due to epistasis, which may continue to direct SARS-CoV-2 evolution into new regions of sequence space. Author summary: SARS-CoV-2 variants evolve in part via mutations in the spike receptor-binding domain (RBD) that impact the ability of this domain to evade binding by neutralizing antibodies while maintaining high-affinity binding to ACE2 receptor. To aid in ongoing viral forecasting and surveillance, we conducted high-throughput measurements of the impacts of all possible amino acid mutations or single-codon deletions on ACE2 binding in the newly evolved Omicron BQ.1.1 and XBB.1.5 variant backgrounds. We find that mutations and deletions are well-tolerated in these domains, consistent with the ongoing evolutionary potential of Omicron sub-variants. We show that the impacts of mutations on ACE2 binding continue to change over time due to the phenomenon of epistasis, though these shifts in mutational effect are less pronounced than epistatic shifts described in earlier variants of concern. Nonetheless, we show that this epistasis continues to enable SARS-CoV-2's exploration of new mutational combinations as it evolves into new regions of sequence space, highlighting the ongoing evolutionary potential this virus will continue to exhibit. [ABSTRACT FROM AUTHOR]