Abstract Ergot alkaloid consumption is detrimental to cattle as it negatively impacts several physiological and performance parameters. The objective of this study was to evaluate changes in nutritional intake and different physiological and performance parameters of heifers consuming an ergot alkaloid-infected ration. Purebred Angus heifers (216.3 ± 6.1 kg; 9 to 11 mo of age; n = 36) were randomly separated and fed either an endophyte-infected (EI) or endophyte-free (EF) total mixed ration (TMR) for 49 d. On d 1, iButton temperature data loggers were inserted intravaginally to record temperature on a 20-min frequency throughout the entire study. Individual feed and water intake was measured utilizing the Vytelle Sense system. Hourly environmental temperature and relative humidity measurements were utilized to calculate the temperature-humidity index (THI) and define exposure to heat stress as Thermoneutral (NO-HS), Mild (MILD-HS) and Moderate (MOD-HS). Pulmonary arterial pressure (PAP) was measured every 20 d to assess its response to ergot alkaloid and heat stress exposure. Additionally, weekly measurements were collected to monitor growth and physiological responses to EI-TMR intake. Data were analyzed using a MIXED procedure of SAS with repeated measures. The effects of treatment, day, THI and its interactions were evaluated for body weight (BW), average daily gain (ADG), body condition score (BCS), hair shedding score (HSS), vaginal temperature (VT), feed intake (FI), water intake (WI) and PAP. EF heifers had significantly less HSS and greater BW, ADG, and BCS than EI heifers over time (P < 0.0001). EF heifers also had lower VT than EI heifers (39.5 ± 0.1 vs 40.1 ± 0.1° C; P < 0.0001) and had reduced daily WI (8.3 ± 0.4 vs 9.4 ± 0.4 L; P < 0.0001). Moreover, WI was also found to be positively correlated to THI, as both EF and EI groups significantly increased (P < 0.0001) their WI as THI increased from NO-HS (5.9 ± 0.6 vs 7.4 ± 0.6 L) to MILD-HS (9.4 ± 0.6 vs 10.8 ± 0.6 L) and MOD-HS (12.8 ± 0.6 vs 13.4 ± 0.6 L). EF heifers also had greater daily FI than EI heifers (18.8 ± 0.6 vs 12.9 ± 0.6 kg; P < 0.0001), and FI was also affected by THI as intake in both EF and EI groups decreased when transitioning from NO-HS (21.3 ± 0.6 vs 14.6 ± 0.6 kg) to MILD-HS (16.4 ± 0.6 vs 11.1 ± 0.6 kg; P < 0.0001). PAP results tended to differ between groups (29.6 ± 0.6 vs 31.1 ± 0.6 mm Hg; P = 0.0954) and increased in both EF and EI groups when transitioning from MILD-HS (27.2 ± 0.9 vs 26.2 ± 0.9 mm Hg) to NO-HS (34.8 ± 0.9 vs 36.4 ± 0.9 mm Hg; P = 0.0147). Based on these data, exposure to ergot alkaloids negatively affects animal performance as it decreases ADG, BCS and increases HSS and VT, and it also increases daily WI and reduces daily FI. Furthermore, PAP, WI and FI were also negatively impacted by changes in THI and exposure to heat stress. Additional research is necessary to understand the interactions between these variables to identify efficiency parameters.