Inflammation and coagulation are the critical responses to infection that include leukocytes, platelets, and vascular endothelial cells responding in concert to eradicate the invading pathogen. In sepsis, a variety of cell surface receptors, including toll-like receptors, Fcγ-receptors, G-protein-coupled receptors, and adhesion receptors, detect the pathogens and elicit thromboinflammatory responses. Concurrently, the molecular patterns released from host damaged cells accelerate the immune responses through binding to the same pattern recognition receptors. Cytokines, chemokines, and extracellular vesicles are important mediators for amplifying the responses to distant cells as part of the systemic response to infections. At the same time, cells communicate with each other via direct contact, adhesion molecules, paracrine mediators, and tunneling nanotubes, which are important for regulating inflammation and thrombus formation. Despite increasing attention to immunothrombosis in sepsis, these close communication systems are less understood but play a critical role in host defense mechanisms. In this review, cellular activation and direct intercellular communication systems in sepsis with a focus on the coagulation response will be considered.