Sepsis in interstitial lung disease (ILD) patients presents unique ICU challenges due to compromised lung reserve and progressive fibrosis. Standard fluid resuscitation must be cautiously balanced to avoid worsening pulmonary edema and hypoxemia. Mechanical ventilation is often difficult, as high pressures can exacerbate lung injury; low tidal volume and lung-protective strategies are essential. Immunosuppressive therapies commonly used in ILD may mask infection signs and increase vulnerability to sepsis. Early broad-spectrum antibiotics, vigilant monitoring, and individualized hemodynamic support are critical. Multidisciplinary care, including early palliative input, is vital, as prognosis is often poor, and aggressive interventions may require ethical consideration.