Objective To explore the effects of virtual reality (VR) at the latent stage combined with epidural block on the analgesic effect, anxiety, depression and labor stress for primiparas during the perinatal period. Methods According to the random number table method, 130 primiparas were divided into two groups (n=65): group A which underwent VR at the latent phase combined with epidural block at the active phase, and group B which underwent epidural block at the active phase. For group A, VR started when the cervix was 1 cm dilated and intervened for 30 min, followed by epidural analgesia when the cervix was 3 cm dilated. For group B, epidural analgesia was performed when the cervix was dilated to 3 cm. Their Numerical Rating Scale (NRS) scores were measured when the cervix was dilated to 1 cm (T0), 30 min after 1 cm cervical dilatation (T1), 1 h after 1 cm cervical dilatation (T2), before epidural analgesia (T3), 10 min (T4), 30 min (T5), 1 h (T6), and 2 h (T7) after analgesia, and at full dilatation (T8). Their State‑Trait Anxiety Inventory (STAI) scores [including State Anxiety Inventory (S‑AI) scores and Trait Anxiety Inventory (T‑AI) scores] were recorded at T0, T1, T5 and 2 h after delivery (T9). Their Edinburgh Postnatal Depression Scale (EPDS) scores at T0, T1, T5 and 3 days after delivery (T10) were recorded. The levels of cortisol (COR), interleukin‑6 (IL‑6) in the saliva and umbilical artery blood at T0, T1 and T9 were detected by enzyme‑linked immunosorbent assay (ELISA). The duration of labor, consumption of anesthetics, the times of patient controlled analgesia (PCA) pressing and postpartum satisfaction were recorded. Results Compared with group B: group A presented remarkable decreases in NRS scores at T1 and T2, S‑AI scores at T1 and T5, T‑AI scores at T1, EPDS scores at T1 and T10, the levels of salivary COR and IL‑6 at T1 (P<0.05), and increases in postpartum satisfaction (P<0.05). Compared with those at T0: group A presented significant decreases in NRS scores at T1‒T8, S‑AI scores and T‑AI scores at T1, T5 and T9, EPDS scores at T10, and the levels of salivary COR and IL‑6 at T1 and T9 (P<0.05); while group B showed significant decreases in NRS scores at T3‒T8, S‑AI scores and T‑AI scores at T5 and T9 , and the levels of salivary COR and IL‑6 at T9 (P<0.05). There was no statistical difference in the levels of COR and IL‑6 in the umbilical artery blood, the duration of labor, the consumption of anesthetics and the times of PCA pressing between two groups (P>0.05). Conclusions The application of VR at the latent phase combined with epidural block for labor analgesia can effectively alleviate pain, anxiety, depression and labor stress during the perinatal period, so as to improve postpartum satisfaction.