Emerging evidence indicates an intricate relationship between the SARS-CoV-2 infection and Multi-Organ Dysfunctions (MODs). Here, we have investigated the role of the Secretome of the SARS-CoV-2 infected pancreas and mechanistically linked it with the multi-organ dysfunction using the scRNA-seq analysis. We found that acinar-specific PRSS2, REG3A, REG1A, SPINK1, and ductal-specific SPP1, MMP7 genes are upregulated in alpha, beta, delta, and mesenchyme cells. Using extensive documented experimental evidence, we validated the association of upregulated pancreatic Secretome with coagulation cascade, complement activation, renin angiotensinogen system dysregulation, endothelial cell injury and thrombosis, immune system dysregulation, and fibrosis. Our finding suggests the influence of upregulated Secretome on multi-organ systems such as Nervous, Cardiovascular, Immune, Digestive, and Urogenital systems. In addition, we report that the secretory proteins IL1B, AGT, ALB, SPP1, CRP, SERPINA1, C3, TFRC, TNFSF10, and MIF are associated with diverse diseases. Thus, suggest the role of the pancreatic Secretome in SARS-CoV-2 associated MODs.