This work was undertaken to investigate some neonatal physiological aspects and their relations with growth rate and survival over the first month of life in prolific D’man sheep by analysing data from a total of 312 lambs. Glucose, protein, cholesterol and triglycerides plasma levels were low at 1–12 h of birth and increased over the first 3 days. Rectal temperature increased as well and a significant effect of year and season of birth was observed, where summer-born lambs had higher rectal temperature both at 24–36 h and 48–60 h of age compared to winter-born lambs. Also, lambs born from older ewes (3–5 years) had higher rectal temperature at 1–12 h than lambs born from younger ewes (<2 years). Winter-born lambs had higher glucose plasma level at 48–60 h of birth than summer-born lambs which had the highest protein plasma level at all time points measured. Birth weight influenced neonatal physiology with heavy lambs having higher rectal temperature, glucose, cholesterol and cortisol plasma levels at 1–12 h of birth than medium and light lambs. Accordingly, quadruplets had the lowest rectal temperature at all time points measured compared to singles, twins and triplets. Twins had higher glucose and protein plasma levels at 1–12 h and 24–36 h of birth than triplets, quadruplets and quintuplets. Birth weight was negatively related to cortisol plasma levels at 24–36 h and 48–60 h of birth. Average daily weight gain over 10 days was positively related to glucose plasma level and rectal temperature, and inversely related to cortisol plasma level at all points measured. Average daily gain weight between 10 and 30 days was also positively related to glucose plasma level and inversely related to cortisol plasma level. Finally, it was found that rectal temperature, glucose and protein plasma levels were higher in lambs that survived beyond one month of age in comparison to those that died. The main outcome of this study is that smaller triplets and quadruplets have lower rectal temperature and metabolites plasma level than twin- and single-born lambs during the first 3 days of life and this impairs their chance of survival. These physiological traits are reliable indicators for health status in prolific D’man sheep and can be exploited in order to improve lamb production.