Nephrotic syndrome (NS) in children is associated with spontaneous bacterial infections, including peritonitis as well as cellulitis secondary to chronic third-spacing of intracellular fluid. Typical pathogens that cause cellulitis in these patients are gram-positive bacteria whereas gram-negative organisms are uncommon. We report a case of Escherichia coli bacteremia with associated rapidly progressive cellulitis in an 11-year-old child with newly diagnosed NS, who had only recently started steroid therapy. Our case highlights the multifactorial effects of NS on the immune system that result in a predisposition towards infection. It also underscores the importance of a broad approach to neuro-atypical children with common clinical complaints.