Subsets of lymphoid stromal cells (LSC), including the fibroblastic reticular cells (FRC) create a network on which immune cells migrate in lymphoid organs. FRC also express chemokines and cytokines that attract naïve T cells and dendritic cells (DC) and contribute to homeostasis in the lymph node (LN). Inflammation triggers lymph node swelling and is accompanied by the expansion of the LSC network. It has been suggested that DC trigger FRC stretching while entry of naive T cells in the LN triggers the expansion of the FRC network. Yet, relatively little is known about the behaviour of LSC during infections, or to what degree pathogens influence LSC responses and functions. We found that local infection with herpes simplex virus (HSV) induced remodeling of the LSC network in the draining LN (dLN), characterized by expansion of FRC. In contrast, local infection with lymphocytic choriomeningitis virus (LCMV) induced abrogated LN hypertrophy and poor FRC expansion. Co-infection of mice with LCMV and HSV, or induction of systemic inflammation during HSV infection, inhibited LSC expansion in the dLN. LCMV infection induced a systemic lymphopaenia and reduced lymphocyte recruitment to the dLN. Reduced lymphadenopathy induced by inflammation or following FTY720 treatment during HSV infection did not alter antigen-specific T cell responses. In contrast, B cell responses to HSV infection were suppressed by systemic inflammation. Blockade of type I interferon receptor partially restored LSC expansion and B cell responses in dLN during co-infection. These data suggest that systemic inflammation alters local lymph node responses, suppressing stromal cell expansion and inhibiting B cell responses.