Background Assessing the severity of transferred neonates at admission can improve resource allocation. This study evaluated the role of TOPS (illness severity score including temperature, oxygen saturation, skin perfusion and blood sugar) in predicting mortality in neonates transferred by ambulance in a low-resource setting. Methods The study was conducted at Beira Central Hospital (Mozambique). Infants who were transferred by ambulance to the Neonatal Intensive Care Unit between 16th June and 16th October 2021 were included. The association between TOPS and mortality was investigated with a logistic regression model. Receiver-operating characteristics (ROC) curve was derived for TOPS; area under the ROC curve, sensitivity and specificity were calculated. Results In-transport mortality was 2/198 (1.0%) and in-hospital mortality was 75/196 (38.3%). Median gestational age and birthweight were 38 weeks and 2600 g. Main causes of admission were asphyxia (29.3%), prematurity (25.3%) and sepsis (22.7%). Hypothermia and oxygen desaturation at admission were 75.8% and 32.3%. TOPS ≥ 1 was associated with increased mortality risk (odds ratio 7.06. 95% confidence interval 1.90 to 45.82), with 0.97 sensitivity and 0.26 specificity. Conclusions The high mortality rate calls for interventions and quality initiative studies to improve the transfer process and the conditions at admission. TOPS can be used to identify neonates at risk of mortality and concentrate efforts of health care providers. Interventions preventing hypothermia and oxygen desaturation should be implemented in pre-transport stabilization and care during transport.