Nesfatin-1, ghrelin and leptin, secreted mainly from the hypothalamus, gastrointestinal tract and adipose tissue, may be related with various metabolic parameters viz. age, body weight, productive performance, DMI, plasma metabolites. They may act on the central nervous system to regulate initiation of puberty. Present study was aimed at finding relationships between nesfatin-1, ghrelin, leptin, and age at onset of puberty, body weight (BW), dry matter intake (DMI) and plasma metabolites in Murrah buffalo heifers. For the present study, thirteen pubertal Murrah buffalo heifers, presenting ovary with an identifiable corpus luteum (CL), and plasma progesterone (P4) concentration ≥1 ng/ml were selected. Blood samples were collected fortnightly until first signs of heat appeared. Nesfatin-1 was positively and significantly (P<0.01) correlated with BW, progesterone, DMI. Correlation was positive and significant (P<0.05) with average daily gain (ADG). However, correlation of nesfatin-1 was negative and significant (P<0.01) with glucose, non-esterified fatty acids (NEFA) and age at puberty. Ghrelin was significantly (P<0.01) and positively correlated with glucose and NEFA. However, it was significantly and negatively correlated with progesterone, BW and DMI. Leptin was significantly (P<0.05) and positively correlated with BW, progesterone, and DMI but negatively correlated with glucose and NEFA. The present study revealed that nesfatin-1, ghrelin and leptin may regulate the age at onset of puberty through regulating the body weight, DMI and plasma progesterone level.