Pulse oximetry is widely used in medical settings and in everyday life for the estimation of peripheral blood oxygen saturation (SpO2). However, SpO2 response measured on the peripheral parts of the body (such as fingers and wrists) has a time lag compared to measuring on the forehead. In addition, current devices are centimeter‐thick, making seamless integration with the body difficult, and hindering continuous monitoring. Here a design, fabrication, and evaluation of a SpO2 and heart rate sensor based on flexible hybrid electronics (FHE) is presented. The marriage of flexible electronics with high‐performance commercially available integrated circuit (IC) chips makes advanced sensing, data processing, and wireless data transmission functionalities possible on a thin (1.6 mm) and flexible form that can be attached to various parts of the body. Differently from most devices using FHE, here a cost‐efficient and mass‐production compatible multilayer screen‐printing process for making the interconnection circuitry is described in detail, including topographic analysis. By optimizing the printing steps, interconnecting lines vertically traversing up to five printed layers over several tens of micrometers can be fabricated, increasing the spatial density. The device reliably detects hypoxemia, and when applied on the forehead, changes in SpO2 appear >10 s earlier compared to a finger‐based medical‐grade device.