Numerous studies have reported important observations about the composition and functional alterations of immune cells in animal aging models. However, animal models fail to recapitulate the human immune environment adequately. What we know about human immune cells is primarily based on flow cytometric analysis, relying on previously described markers for pooled cell populations. These analytical methods are too biased to reveal information on selected and not all cells or cell populations. Single-cell technologies open new avenues in many research fields but are particularly important for analyzing human cells in aging and diseases in an unbiased and global fashion (He et al., 2020; Wang et al., 2020; Zhang et al., 2020). Using scRNA-seq, recent studies have reported transcriptomic and functional changes in immune cells during aging in mouse cells and tissues such as the central nervous system (Mrdjen et al., 2018), macrophages in brain (Martinez-Jimenez et al., 2017; Van Hove et al., 2019), TCs in spleen (Dulken et al., 2019), and hematopoietic stem cells in bone marrow (Leins et al., 2018). Recently, our group revealed how aging affects the immune system in rats (Ma et al., 2020). For humans, mass cytometry analysis showed that aging increased epigenetic variations in circulatory immune cells (Cheung et al., 2018). However, a comprehensive atlas of immune cell aging has not yet been constructed. Here, we depicted such an atlas from PBMCs harvested from healthy young and old research subjects and young and old patients with COVID-19. First, scRNA-seq and CyTOF reveal that aging causes cell compositional changes at the cell type and subtype levels. Second, our study provides the first high-quality analysis of TCR and BCR repertoires in young and aged adults at a single-cell resolution. Third, our study provides the first chromosomal accessibility profiles of major immune cells in young and aged healthy research subjects at the single-cell level. Combined with several novel single-cell methodologies, this study represents a state-of-the-art unbiased and systematic analysis of human immune cell aging.