Study objectives were to evaluate the impact of early life thermal stress (ELTS) on thermoregulation, stress response, and intestinal health of piglets subjected to a future heat stress (HS) challenge during simulated transport. From d 7 to 9 post-farrowing, 12 first-parity sows and their litters were exposed to thermoneutral (ELTN; 25.4 ± 1.1 °C w/heat lamp; n = 4), HS (ELHS; cycling 32-38 °C w/heat lamp; n = 4), or cold stress (ELCS; 25.4 ± 1.1 °C w/no heat lamp; n = 4) conditions, and then from d 10 until weaning all piglets were exposed to thermoneutral (TN) conditions (25.3 ± 1.9 °C w/heat lamp). During the ELTS period, respiration rate, rectal temperature (TR), and skin temperature (TS) of three mixed-sex piglets per dam were monitored daily (0800, 1200, 1600, 2000 h). At 13 ± 1.3 d of age, temperature recorders were implanted intra-abdominally into all piglets. At weaning (20.0 ± 1.3 d of age), piglets were bled and then herded up a ramp into a simulated transport trailer and exposed to HS conditions (cycling 32-38 °C) for 8 h. During the 8 h simulated transport, core body temperature (TC) and TS were assessed every 15 min. After the simulated transport, piglets were unloaded from the trailer, bled, weighed, and then housed individually in TN conditions (28.5 ± 0.7 °C) for 7 d. During this time, ADFI and ADG were monitored, blood samples were taken on d 1, 4, and 7, and piglets were video-recorded to assess behavior. Piglets were sacrificed on d 8 post-simulated transport and intestinal morphology was assessed. Data were analyzed using PROC MIXED in SAS 9.4. In the ELTS period, piglet TR was increased overall (P = 0.01) in ELHS (39.77 ± 0.05 °C) compared to ELTN (39.34 ± 0.05 °C) and ELCS (39.40 ± 0.05 °C) litters. During simulated transport, TC was greater (P = 0.02) in ELHS (40.84 ± 0.12 °C) compared to ELTN (40.49 ± 0.12 °C) and ELCS (40.39 ± 0.12 °C) pigs. Following simulated transport, BW loss was greater (P = 0.01; 40%) for ELHS compared to ELTN and ELCS pigs and ADFI was reduced (P = 0.05; 28.6%) in ELHS compared to ELTN pigs. Sitting behavior tended to be increased (P = 0.06; 47.4%) in ELHS vs. ELCS or ELTN pigs. Overall, circulating cortisol was greater for ELHS (P ≤ 0.01; 38.8%) compared to ELCS and ELTN pigs. Goblet cells per villi were reduced (P = 0.02; 20%) in the jejunum of ELHS vs. ELCS and ELTN pigs. In summary, ELHS reduced thermotolerance and increased the future stress response of piglets compared to ELCS and ELTN.