Presence of antibiotics in raw milk threatens human health and dairy production. Heat treatments are expected to inactivate various pathogens or reduce the amount of other undesired substances such as antibiotics before milk reach consumers. As a common part of cephalosporins’ molecular structure, β-lactam ring makes cephalosporins susceptive to chemical reaction. Hence, cephalosporins are very likely to experience decrease once heated. To date, few information about cephalosporins’ stability during conventional dairy process such as high temperature short time pasteurization (HTST) and ultrahigh temperature process (UHT) has been reported. This study was designed to study the effects of HTST and UHT on cephalosporins. So heat treatment were performed on raw milk samples spiked with 5 cephalosporins—cefoperazone (PER), cefquinome (QUI), cephapirin (PIR), ceftiofur (TIO), cefazolin (ZOL)—on the level of maximum residues limits (MRLs). Of these treatments, 65°C/15s was used for preheating raw milk, 20M Pa for homogenization, 75°C/15s for HTST and 140°C/4s for UHT. Concentration of 5 cephalosporins in milk was determined by UPLC-MS/MS simultaneously before and after heat treatment. Recovery test was conducted to validate the analytical methods used in this study for determination of 5 cephalosporins in our lab. SAS 9.2 statistical software package were applied to carry out the statistical analysis. Data of recovery ranges from 85.8% to 99.8% with RSD lower than 10%, which demonstrates good recovery was obtained. Degradation percentages of cephalosporins obtained after HTST is as following: 2.6% for ZOL, 8.6% for PIR, 12.2% for QUI and 12.3% for TIO with the highest 20.5% for PER. Whereas UHT process showed higher reduction level of cephalosporins in all cases. As is shown, cephalosporins’ loss is 15.7% for PIR, 36.3% for PER, 43.9% for QUI, 50.0% for TIO with the highest 77.4% for ZOL after UHT. It is noteworthy that degradation results obtained in our work is higher than the previous data predicted by M. Roca (2011) using the prediction model based on the kinetic equation. In addition, the effect of HTST and UHT displays significant difference (P < 0.01). In conclusion, cephalosporins studied in this work is resistant to HTST but is unstable in UHT.