A spring-loaded exoskeleton design was recently developed for the upper limbs of physically challenged and healthy people, enabling them to move multiple joints of the upper limbs on different motion planes. A four-degree-of-freedom design allows the exoskeleton arms to perform shoulder abduction–adduction, flexion–extension, internal–external rotation, and elbow flexion–extension motions. The purpose of this study was to compare the muscle activation levels during upper limb resistance exercises that were performed using dumbbells and a spring-loaded exoskeleton. The upper limb resistance exercises were conducted under varying conditions, using 1- and 3-kg applied loads, and with 1- and 2-s motion speeds. Six healthy participants performed three movements: shoulder abduction–adduction, shoulder flexion–extension, and elbow flexion–extension. Dumbbells and a spring-loaded upper limb exoskeleton were used as resistance sources. Surface electromyography was applied to analyze participant muscle functions; surface electrodes were placed over the anterior deltoid, middle deltoid, posterior deltoid, pectoralis major, biceps brachii, triceps brachii, upper trapezius, and supraspinatus. All results were presented as normalized surface electromyography amplitudes. Our study findings suggest that muscle activation levels during the three designated upper limb resistance exercises have consistent patterns, and that the difference between using dumbbells and the spring-loaded exoskeleton was mostly nonsignificant; therefore, the spring-loaded exoskeleton is able to provide similar training effects to that of dumbbells.