Strongyloidiasis develops from the infection with Strongyloides stercoralis (Family: Strongylidae) and was recently considered a neglected tropical disease by the World Health Organization due to its global distribution and high burden of infection. Here, we present the cases of two patients under corticosteroid therapy after neurosurgical surgery who developed septic shock-like hyperinfection syndrome due to disseminated strongyloidiasis. The first case is a 77-year-old man from Cape Verde who was diagnosed with an extra-axial right parietal brain mass. He was given dexamethasone and was submitted to a biparietal craniotomy. His condition deteriorated and he was admitted to the intensive care unit (ICU), where he was diagnosed with disseminated strongyloidiasis with hyperinfection. Anthelmintic treatment and corticosteroid therapy were rapidly tapered and stopped. Neurological dysfunction persisted and the patient was transferred to the ward. The patient had died after complications of hospital-acquired pneumonia. The second case is a 47-year-old man from Guinea-Bissau who was diagnosed with a space-occupying lesion in the right temporal region and started treatment with dexamethasone. He underwent a craniectomy with partial excision of the lesion (high-grade glioma). Later his neurologic state worsened, and he was diagnosed with septic shock and hospital-acquired pneumonia. He was admitted to the ICU, the diagnosis of disseminated strongyloidiasis and hyperinfection syndrome was made and he initiated treatment with ivermectin and albendazole. Corticosteroid therapy was tapered. The patient's clinical status deteriorated, and multiple opportunistic infections were diagnosed during the ICU stay, which lead him to die. Clinicians should have a high index of suspicion when in the presence of corticosteroid-treated patients with sepsis. Preventive strategies and subsequent treatment should be considered in patients with a risk of acquisition or dissemination. Treating severe strongyloidiasis is still a clinical challenge and a delayed diagnosis can significantly worsen the outcomes of the patients affected, as seen in the presented cases.