Aim and background: The recent Nigerian human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) Indicator and Impact Survey (NAIIS) has revealed a decline in the national seroprevalence of pediatric HIV infection. This study aimed to determine the seroprevalence of pediatric HIV infection in a hospital-based study and to determine the clinical presentations among newly diagnosed children at Federal Medical Centre (FMC), Katsina. Materials and methods: Consecutive new patients aged 2 months to 5 years who presented at the emergency pediatric unit of the hospital were screened for HIV infection. History and physical examination findings were documented for each child. Seropositive children <18 months had their status confirmed using HIV deoxyribonucleic acid polymerase chain reaction (HIV DNA PCR). Results: Of the 508 children screened, four were seropositive for HIV, giving a seroprevalence of 0.8%. Common symptoms in the HIV-infected children were fever (100%), vomiting (75%), poor weight gain (75%), and cough (50%). Common signs in HIV-infected children were oral thrush (75%), skin lesions (75%), generalized lymphadenopathy (50%), and parotid fullness (25%). However, only oral thrush was predictive of HIV infection (p < 0.007). Conclusion: This study reveals a substantial reduction in the seroprevalence of HIV infection among children presenting at the pediatric emergency unit of FMC Katsina. Of the symptoms and signs associated with the infection, only oral thrush was predictive. Clinical significance: The study contributed to knowledge by documenting the seroprevalence of pediatric HIV in FMC Katsina and the clinical features predictive of HIV infection.