Long COVID, or post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC), is characterized by persistent symptoms following COVID-19. This study employs RNA sequencing to explore the transcriptomic profiles of whole blood and peripheral blood mononuclear cells (PBMCs) from long COVID patients and healthy controls. Quality control, alignment, and quantification were performed using publicly available datasets with FastQC, STAR, and FeatureCounts, followed by differential expression and pathway enrichment analyses using DESeq2 and RStudio. PBMC data revealed immune-specific dysregulation, including enriched pathways for ribonucleoprotein biogenesis, oxidative phosphorylation, and cytotoxic immune responses, reflecting mitochondrial dysfunction and immune activation. Whole blood captures broader systemic processes, highlighting oxidative stress, metabolic reprogramming, and cardiovascular pathways. Differential expression revealed hemoglobin-related and mitochondrial genes as central to long-term COVID pathology. These findings illuminate the distinct immune and systemic dysregulation underlying long COVID, providing a basis for biomarker discovery and targeted therapeutic strategies.