There are rising cases of building occupants with health-related challenges such as irritation, asthma, lung infections, headaches, and other allergies. These health conditions sometimes disappear once the occupants live such buildings which are referred to as sick building syndrome (SBS). With the high fatality rate associated with air pollution and Nigeria ranking 4th in the poorest air quality globally, the study assessed SBS from indoor pollution in residential and office spaces. The study utilized a cross-sectional survey research design and employed the use of an air quality detector to measure a 24-h mean measurement of air conditions within the study area. The study was carried out in Zaria, Kaduna State. Statistical tools such as graphs, mean score, analysis of variance (ANOVA), and correlation matrix were used to analyze the dataset. The study showed that the major symptoms associated with SBS from indoor pollution. The indoor conditions that may contribute to SBS in the residential and office spaces were mainly lighting conditions, headroom in the building, and position of windows. While the study reported that the presence of SBS from indoor pollution can lead to increased maintenance, dizziness, and depression/breakdown. The measurement of the indoor pollutants contributing to the SBS among residential and office space occupants showed that PM2.5 and PM10 were mostly above the average 24-h mean standard. The study suggested recommendations to improve indoor air quality and reduce syndromes associated with sick buildings.