Background: This study investigated the effect of low flow cardiopulmonary bypass, circulatory arrest, and selective cerebral perfusion on expression and phosphorylation of selected regulators of cell death and survival in striatum of newborn piglets. Methods: Animals were assigned to sham operation and three experimental groups. The experimental groups were placed on bypass, cooled to 18°C, and subjected to 90 minutes of deep hypothermic circulatory arrest (DHCA), low-flow cardiopulmonary bypass (LFCPB) at mL/(kg · min), or selective cerebral perfusion (SCP) at 20 mL/(kg · min), followed by rewarming and 2 hours of recovery. The oxygen pressure in the microcirculation of the cortex was measured by quenching of phosphorescence. Levels of phosphorylated and total protein were determined by Western blot analysis. Results: Control oxygen pressure was 55 ± 9 mm Hg and decreased during DHCA, LFCPB, and SCP to 1.1 ± 0.6 mm Hg, 9.8 ± 2.3 mm Hg, and 9.3 ± 1.9 mm Hg, respectively (p < 0.001). After DHCA, N-terminal of Bcl-2-associated X protein (N-Bax) levels increased (295% ± 15%, p < 0.01), B-cell leukemia protein (Bcl-2) levels decreased (31% ± 9%, p < 0.01), and phosphorylation level of protein kinase B (pAkt) and extracellular signal-regulated kinase 1/2 (pERK1/2) did not change. After LFCPB and SCP, N-Bax and Bcl-2 levels were unchanged, pAkt levels increased (367% ± 122%, p < 0.05 and 337% ± 47%, p < 0.01, respectively), pERK1 (484% ± 70% and 501% ± 255%, respectively; p < 0.01) and pERK2 (569% ± 128%; p < 0.001 and 494% ± 162%; p < 0.05, respectively) levels increased, and total ERK2 levels also increased (279% ± 90% and 153% ± 44%, respectively, p < 0.05). Conclusions: Stable levels of Bcl-2 and Bax and the increases in pAkt and pERK1/2 after LFCPB and SCP are likely indicators of improved chances for cell survival.